A Preliminary Study of the Potential Molecular Mechanisms of Individual Growth and Rumen Development in Calves with Different Feeding Patterns.

At present, it is common to feed calves with "Concentrate", "Concentrate + hay" and TMR "Total Mixed Rations" feeding patterns in China, which achieved well feeding efficiency, but the three feeding patterns molecular regulation mechanism in actual production is still unclear. The study aimed to explore the most suitable feeding pattern for Chinese Holstein calves to improve the rumen fermentation function and growth performance of calves. In this regard, the interactions between rumen microorganisms and host metabolism were investigated. The rumen volume and weight of calves in the GF group were significantly higher than those in the GFF and TMR groups (p < 0.05), and the rumen pH of calves in the GF group was 6.47~6.79. Metagenomics analysis revealed that the rumen microbiome of GF and GFF calves had higher relative abundances of Methanobrevibacter, Methanosphaera, and Methanolacinia (p < 0.05). Prevotella multisaccharivorax was significantly more abundant in the rumen of GF calves (p < 0.05), indicating that GF group calves had a stronger ability to ferment sugars. Notably, in the pyruvate metabolic pathway, phosphoenolpyruvate carboxylase was significantly up-regulated in GF calves compared with the TMR group, and pyruvate-phosphate dikinase was significantly down-regulated. Metabolomic results showed that Ursodeoxycholic acid was significantly up-regulated in GF calves, and most of the differential metabolites were enriched in Bile secretion pathways. The association analysis study found that the microorganisms of Prevotella and Ruminococcaceae might cooperate with the host, which was helpful for the digestion and absorption of lipids and made the calves have better growth. The three feeding modes had similar effects, but the 'GF' feeding pattern was more beneficial to the individual growth and ruminal development regarding ruminal morphology, contents physiology and microorganisms. Furthermore, the synergistic effect of rumen microorganisms and the host could more effectively hydrolyze lipid substances and promote the absorption of lipids, which was of great significance to the growth of calves.

The effects of differential feeding on ileum development, digestive ability and health status of newborn calves.

Pre-weaning is the most important period for the growth and development of calves. Intestinal morphology, microbial community and immunity are initially constructed at this stage, and even have a lifelong impact on calves. Early feeding patterns have a significant impact on gastrointestinal development and microbial communities. This study mainly analyzed the effects of three feeding methods on the gastrointestinal development of calves, and provided a theoretical basis for further improving the feeding mode of calves. it is very important to develop a suitable feeding mode. In this study, we selected nine newborn healthy Holstein bull calves were randomly selected and divided into three groups (n = 3), which were fed with starter + hay + milk (SH group), starter + milk (SF group), total mixed ration + milk (TMR group). After 80 days of feeding Feeding to 80 days of age after, the ileum contents and blood samples were collected, and the differences were compared and analyzed by metagenomic analysis and serum metabolomics analysis. Results show that compared with the other two groups, the intestinal epithelium of the SH group was more complete and the goblet cells developed better. The feeding method of SH group was more conducive to the development of calves, with higher daily gain and no pathological inflammatory reaction. The intestinal microbial community was more conducive to digestion and absorption, and the immunity was stronger. These findings are helpful for us to explore better calf feeding patterns. In the next step, we will set up more biological replicates to study the deep-seated reasons for the differences in the development of pre-weaning calves. At the same time, the new discoveries of neuro microbiology broaden our horizons and are the focus of our future attention.

High expression of miR-30c-5p in satellite cells of high-fat diet-induced obese rabbits inhibited satellite cell proliferation and promoted differentiation.

It was revealed in our previous study that the expression of miR-30c-5p in the skeletal muscle of rabbits fed high-fat diet was highly expressed. In the present study, we further investigated the function of miR-30c-5p in proliferation and differentiation of skeletal muscle satellite cell (SMSC). The results obtained in the present study showed that the skeletal muscle fibers of the rabbits fed the standard normal diet (SND) were orderly, regular, and uniform after HE staining, however, the muscle fibers of the rabbits fed the high-fat diet (HFD) were generally atrophied, some were arranged disorderly, the intercellular space was enlarged, the nucleus was increased, and the morphology and position were abnormal. Compared with the SND group, it was observed that the weekly weight gain and fat percentage were relatively higher, and also the levels of the serum biochemical indexes such as glucose, cholesterol, and triglyceride increased significantly in the rabbits fed with HFD. In addition, the results after the transfection of miR-30c-5p mimic, mimic NC (negative control), miR-30c-5p inhibitor, and inhibitor NC into the SMSCs showed that the cell counting kit-8 (CCK-8) proliferation experiment suggested that the number of cells in the over expression group was significantly lower than that in the mimic NC group at 48, 72, 96 h of cell proliferation. At 48, 72, 120 h, the number of cells in the inhibitor group was significantly higher than that in the mimic NC group. The number of EdU positive cells decreased significantly in the over expression group compared with the mimic NC group, however, it increased significantly in the inhibitor group compared with the inhibitor NC group. Moreover, compared with the mimic NC group, the myotube area increased significantly in the miR-30c-5p mimic group, whereas it decreased significantly in the miR-30c-5p inhibitor group as compared with the inhibitor NC group. In addition, we found that trinucleotide repeat containing adaptor 6A (TNRC6A) was successfully validated as a target gene for miR-30c-5p. The expression of TNRC6A in the miR-30c-5p mimic group was significantly lower than that in the mimic NC group. It was further observed that the expression of TNRC6A increased significantly in the miR-30c-5p inhibitor group as compared to that in the inhibitor NC group. Taken together, the results obtained in this study showed that miR-30c-5p promotes the differentiation as well as inhibits the proliferation of rabbit skeletal muscle satellite cells, and TNRC6A is a target gene of miR-30c-5p.

Integration of Non-Coding RNA and mRNA Profiles Reveals the Mechanisms of Rumen Development Induced by Different Types of Diet in Calves.

Selecting suitable feed types and understanding the gastrointestinal digestive mechanism are helpful for the growth and health of calves in intensive dairy farming. However, the effects on rumen development of changing the molecular genetic basis and the regulatory mechanism by using different feed types are still unclear. Nine 7-day-old Holstein bull calves were randomly divided into GF (concentrate), GFF (alfalfa: oat grass = 3:2) and TMR (concentrate: alfalfa grass: oat grass: water = 0.30:0.12:0.08:0.50) diet experiment groups. Rumen tissue and serum samples were collected for physiological and transcriptomic analysis after 80 days. The results showed that serum α-amylase content and ceruloplasmin activity were significantly higher in the TMR group, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis ncRNAs and mRNAs were significantly enriched in the pathways of rumen epithelial development and stimulated rumen cell growth, including the Hippo signaling pathway, Wnt signaling pathway, thyroid hormone signaling pathway, ECM-receptor interaction and the absorption of protein and fat. The circRNAs/lncRNA-miRNAs-mRNA networks constructed, including novel_circ_0002471, novel_circ_0012104, TCONS_00946152, TCONS_00960915, bta-miR-11975, bta-miR-2890, PADI3 and CLEC6A, participated in metabolic pathways of lipid, immune system, oxidative stress and muscle development. In conclusion, the TMR diet could improve rumen digestive enzyme activities, stimulate rumen nutrient absorption and stimulate the DEGs related to energy homeostasis and microenvironment balance, and is thus better than the GF and GFF diets for promoting rumen growth and development.

Microbiome, Transcriptome, and Metabolomic Analyses Revealed the Mechanism of Immune Response to Diarrhea in Rabbits Fed Antibiotic-Free Diets.

In this study, diarrhea was induced in rabbits by feeding them antibiotic-free feed. The gut provides important defense against the barriers of the body, of which the duodenum is an important part to help digest food and absorb nutrients. However, the mechanisms underlying the roles of the gut microbiome and fecal metabolome in rabbit diarrhea caused by feeding an antibiotic-free diet have not been characterized. Recently, only a single study has been conducted to further characterize the antibiotic-free feed additives that caused diarrhea in weaned rabbits. The multi-omics techniques, including 16S rRNA sequencing, transcriptome sequencing, and LC-MS analysis, were combined to analyze the gut microbial compositions and functions. They also determined the fecal metabolomic profiles of diarrhea in rabbits caused by feeding antibiotic-free feed. The results showed that the liver, duodenal, and sacculus rotundus tissues of diarrhea rabbits were diseased, the composition of intestinal microbes was significantly changed, the diversity of intestinal microbes was decreased, and the distribution of intestinal microbe groups was changed. Functional analysis based on the cluster of GO and KEGG annotations suggested that two functional GO categories belonged to the metabolism cluster, and five KEGG pathways related to the metabolic pathways were significantly enriched in diarrhea rabbits. Moreover, real-time quantitative PCR (RT-qPCR) was used to verify the significant expression of genes related to diarrhea. Metabolomics profiling identified 432 significantly differently abundant metabolites in diarrhea rabbits, including amino acids and their derivatives. These amino acids were enriched in the tryptophan metabolic pathway. In addition, the functional correlation analysis showed that some altered gut microbiota families, such as Parasutterella, significantly correlated with alterations in fecal metabolites. Collectively, the results suggested that altered gut microbiota was associated with diarrhea caused by antibiotic-free feed additives in weaned rabbit pathogenesis.

The Multi-Omics Analysis Revealed Microbiological Regulation of Rabbit Colon with Diarrhea Fed an Antibiotic-Free Diet.

Diarrhea symptoms appeared after antibiotics were banned from animal feed based on the law of the Chinese government in 2020. The colon and its contents were collected and analyzed from diarrheal and healthy rabbits using three omics analyses. The result of the microbial genomic analysis showed that the abundance of Bacteroidetes and Proteobacteria increased significantly (p-value < 0.01). Transcriptomes analysis showed that differentially expressed genes (DEGs) are abundant in the IL-17 signaling pathway and are highly expressed in the pro-inflammatory pathway. The metabolome analysis investigated differential metabolites (DMs) that were mainly enriched in tryptophan metabolism and bile secretion, which were closely related to the absorption and immune function of the colon. The results of correlation analysis showed that Bacteroidetes was positively correlated with 4-Morpholinobenzoic acid, and 4-Morpholinobenzoic acid could aggravate inflammation through its influence on the bile secretion pathway. The enriched DMs L-Tryptophan in the tryptophan metabolism pathway will lead to the functional disorder of inhibiting inflammation by affecting the protein digestion and absorption pathway. Thus, the colonic epithelial cells were damaged, affecting the function of the colon and leading to diarrhea in rabbits. Therefore, the study provided an idea for feed development and a theoretical basis for maintaining intestinal tract fitness in rabbits.

Microbiomics Revealed the Disturbance of Intestinal Balance in Rabbits with Diarrhea Caused by Stopping the Use of an Antibiotic Diet.

The harmful effects of diarrhea on the growth performance of rabbits have been well documented, but the details of the potential mechanism of intestinal diarrhea when antibiotics are stopped are still unclear. Here, PacBio sequencing technology was used to sequence the full length 16S rRNA gene of the microbiota of intestinal content samples, in order to characterize the bacterial communities in the small intestine (duodenum and jejunum) and large intestine (colon and cecum) in normal Hyplus rabbits and those with diarrhea. The histopathological examination showed that intestinal necrosis occurred in different degrees in the diarrhea group, and that the mucosal epithelium was shed and necrotic, forming erosion, and the clinical manifestation was necrosis. However, the intestinal tissue structure of the normal group was normal. The results revealed that there were significant differences in bacterial communities and structure between the diarrhea and normal groups of four intestinal segments (p < 0.05). In general, 16 bacterial phyla, 144 bacterial genera and 22 metabolic pathways were identified in the two groups. Tax4Fun functional prediction analysis showed that KEGG related to amino acid metabolism and energy metabolism was enriched in the large intestines of rabbits with diarrhea, whereas lipid metabolism was more abundant in the small intestine of rabbits with diarrhea. In conclusion, the change in the relative abundance of the identified dominant microbiota, which could deplete key anti-inflammatory metabolites and lead to bacterial imbalance and diarrhea, resulted in diarrhea in Hyplus rabbits that stopped using antibiotics.

The Multi-Omics Analysis Revealed a Metabolic Regulatory System of Cecum in Rabbit with Diarrhea.

With the comprehensive prohibition of antibiotics in the feed industry in China, the incidence of diarrhea in rabbits increased, such as loss of appetite, vomiting, and excretion of atheromatous feces. In order to explore the pathological and the molecular mechanisms of the diarrhea in the rabbitry fed with antibiotic-free diet, we used microbial metagenomics, transcriptome, and non-targeted metabolomics sequencing. The results showed that the Firmicutes level was significantly decreased (p < 0.001) and the Proteobacteria level was significantly increased (p < 0.05). The functional enrichment of cecum revealed that most differentially expressed genes (DEGs) were expressed in immune, inflammatory, and metabolic processes. The enrichment of the cecal fecal metabolites focused on the bile secretion, antifolate resistance, and tryptophan metabolism pathways, which are mainly associated with inflammation. The results of correlation analysis showed that Fournierella was positively correlated with myricetin, ursolic acid, and furtherly might cause bile secretion and tryptophan metabolism disorder, aggravate intestinal inflammation, change intestinal permeability, and reduce host immunity, leading to diarrhea in rabbits. This study provides a theoretical basis for illustrating the reason for diarrhea and developing new feeds for the health of rabbits.

Environmental enrichment changes rabbits' behavior, serum hormone level and further affects cecal microbiota.

Many studies have shown that stress is associated with gut microbiota. Environmental enrichment (EE) could reduce stress in farm animals; however, limited information is available on the microbial community composition in rabbits raised with or without EE. This study aimed to identify EE influences on the behavior, serum hormonal levels, and cecal microbiota of rabbits. Two hundred Rex rabbits were segregated randomly within four cohorts (n = 50); reared for 76 d within standardized enclosures (non-enriched) or within cages containing a willow-stick (WS), rubber-duck (RD), or a can of beans (CB). The rabbits' ingestive, rest, locomotion, exploratory, grooming, and abnormal behavior were observed. The serum hormone levels for rabbits were measured, and cecal specimens were sequencedfrom the V3-V4 region using 16S rRNA amplicons. Environmental enrichment increased feeding and drinking time, promoted exploratory behavior, and reduced abnormal behavior in rabbits. Insulin-like growth factor 1(IGF-1) levels of the enriched cohorts were elevated in comparison to the control cohort. Serum cortisol level for CB cohort was markedly reduced in comparison to the control cohort (p < 0.05), while dopamine levels for CB cohort peaked. Further, we found that EE mainly affected the dominant microbiota. Several families, such as Erysipelotrichaceae, Tannerellaceae, Enterobacteriaceae, Burkholderiaceae, and Prevotellaceae were markedly reduced within the CB cohort. Bacteria such as Alloprevotella, Bifidobacterium, Enterobacteriaceae, Parabacteroides, and Erysipelatoclostridium were identified as having negative associations with the presence of serum cortisol. EE influenced rabbit behavior and serum hormonal levels, and CB enrichment was the most suitable for rabbits. Further, cecal microbiota composition and diversity were affected by CB enrichment. These findings suggested that CB could be considered for use in rabbit husbandry.

Transcriptomics Analysis Reveals the Immune Response Mechanism of Rabbits with Diarrhea Fed an Antibiotic-Free Diet.

China officially promulgated the announcement of banning the use of antibiotics in the animal industry in 2020. However, the prohibition of antibiotics in the animal industry would reduce the feed conversion rate and increase the mortality of animals. In order to obtain information about the pathogenesis and host immune response of rabbits with diarrhea after being fed an antibiotic-free diet, we first analyzed the intestinal tissue sections of rabbits. Secondly, the gene expression differences of rabbit intestinal segments were analyzed by high-throughput sequencing. Our analysis identified 168, 593, 2069, 334, 321, and 1423 DEGs in the comparison groups S_Z (the duodenum of healthy rabbits) vs. S_B (diarrhea in the duodenum of rabbits), K_Z (healthy rabbit jejunum) vs. K_B (rabbits with diarrhea in the jejunum), H_Z (healthy rabbit ileum) vs. H_B (rabbits with diarrhea in the ileum), M_Z (healthy cecum of rabbits) vs. M_B (rabbits with diarrhea in the cecum), J_Z (healthy rabbit colon) vs. J_B (colon of rabbits with diarrhea), and Z_Z (healthy rabbit rectum) vs. Z_B (rectum of rabbits with diarrhea), respectively. The reproducibility and repeatability of the results were validated by RT-qPCR. Enrichment analyses of GO annotations and KEGG pathways revealed the host DEGs that are potentially related to acute inflammation, stress response, tissue dehydration, adaptive immune response, protein binding, activation of related enzymes, migration of immune cells, and so on. In this descriptive study, our findings revealed the changes in the host transcriptome expression profile after feeding an antibiotic-free diet and suggested that feeding an antibiotic-free diet alters the host's metabolic network and the expression of antiviral proteins, which provides a theoretical basis for further study on the immune response of animals fed an antibiotic-free diet.

Molecular Profiling of DNA Methylation and Alternative Splicing of Genes in Skeletal Muscle of Obese Rabbits.

DNA methylation and the alternative splicing of precursor messenger RNAs (pre-mRNAs) are two important genetic modification mechanisms. However, both are currently uncharacterized in the muscle metabolism of rabbits. Thus, we constructed the Tianfu black rabbit obesity model (obese rabbits fed with a 10% high-fat diet and control rabbits from 35 days to 70 days) and collected the skeletal muscle samples from the two groups for Genome methylation sequencing and RNA sequencing. DNA methylation data showed that the promoter regions of 599 genes and gene body region of 2522 genes had significantly differential methylation rates between the two groups, of which 288 genes had differential methylation rates in promoter and gene body regions. Analysis of alternative splicing showed 555 genes involved in exon skipping (ES) patterns, and 15 genes existed in differential methylation regions. Network analysis showed that 20 hub genes were associated with ubiquitinated protein degradation, muscle development pathways, and skeletal muscle energy metabolism. Our findings suggest that the two types of genetic modification have potential regulatory effects on skeletal muscle development and provide a basis for further mechanistic studies in the rabbit.

Untargeted Metabolomic Characteristics of Skeletal Muscle Dysfunction in Rabbits Induced by a High Fat Diet.

Type 2 diabetes and metabolic syndrome caused by a high fat diet (HFD) have become public health problems worldwide. These diseases are characterized by the oxidation of skeletal muscle mitochondria and disruption of insulin resistance, but the mechanisms are not well understood. Therefore, this study aims to reveal how high-fat diet causes skeletal muscle metabolic disorders. In total, 16 weaned rabbits were randomly divided into two groups, one group was fed a standard normal diet (SND) and the other group was fed a high fat diet (HFD) for 5 weeks. At the end of the five-week experiment, skeletal muscle tissue samples were taken from each rabbit. Untargeted metabolomic analysis was performed using ultra-performance liquid chromatography combined with mass spectrometry (UHPLC-MS/MS). The results showed that high fat diet significantly altered the expression levels of phospholipids, LCACs, histidine, carnosine, and tetrahydrocorticosterone in skeletal muscle. Principal component analysis (PCA) and least squares discriminant analysis (PLS-DA) showed that, compared with the SND group, skeletal muscle metabolism in HFD group was significantly up-regulated. Among 43 skeletal muscle metabolites in the HFD group, phospholipids, LCACs, histidine, carnosine, and tetrahydrocorticosteroids were identified as biomarkers of skeletal muscle metabolic diseases, and may become potential physiological targets of related diseases in the future. Untargeted metabonomics analysis showed that high-fat diet altered the metabolism of phospholipids, carnitine, amino acids and steroids in skeletal muscle of rabbits. Notably, phospholipids, LCACs, histidine, carnopeptide, and tetrahydrocorticosteroids block the oxidative capacity of mitochondria and disrupt the oxidative capacity of glucose and the fatty acid-glucose cycle in rabbit skeletal muscle.

Untargeted Metabolomics Reveals Intestinal Pathogenesis and Self-Repair in Rabbits Fed an Antibiotic-Free Diet.

The prohibition of the use of growth-promoting drug additives in feeds was implemented in China in 2020. However, rabbits can experience symptoms of intestinal disease, such as diarrhea and flatulence, when switching from standard normal diets with antibiotics to antibiotic-free diets. The molecular mechanisms related to the occurrence of these diseases as well as associated physiological and metabolic changes in the intestine are unclear. Thus, the objectives of this study were to study the pathogenesis of intestinal inflammation using untargeted metabolomics. This was done to identify differential metabolites between a group of antibiotic-free feed Hyplus rabbits (Dia) whose diet was abruptly changed from a standard normal diet with antibiotics to an antibiotic-free diet, and an antibiotic diet group Hyplus rabbits (Con) that was fed a standard normal diet with antibiotics. Morphological damage to the three intestinal tissues was determined through visual microscopic examination of intestinal Dia and Con tissue samples stained with hematoxylin and eosin (HE). A total of 1969 different metabolites were identified in the three intestinal tissues from Dia and Con rabbits. The level of 1280 metabolites was significantly higher and the level of 761 metabolites was significantly lower in the Dia than in the Con group. These differential metabolites were involved in five metabolic pathways associated with intestinal inflammation (tryptophan metabolism, pyrimidine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, lysine degradation, and bile secretion). Rabbits in the Dia group developed metabolic disorders that affected the intestinal microbiota and changed the permeability of the intestinal tract, thereby triggering intestinal inflammation, affecting feed utilization, reducing production performance, and activating the intestinal tract self-repair mechanism. Thus, the abrupt transition from a diet with antibiotics to an antibiotic-free diet affected the structure and metabolism of the intestinal tract in Hyplus rabbits. Consequently, to avoid these problems, the antibiotic content in a rabbit diet should be changed gradually or alternative antibiotics should be found.

Heat Stress Affects Faecal Microbial and Metabolic Alterations of Rabbits.

Heat stress can impair the rabbit immune system, induce oxidative stress, and cause many complications. These diseases are characterized by metabolic disorders, but the underlying mechanism is unknown. As a result, the current research determines the effects of HS on intestinal microorganisms in rabbits and the metabolic pathway disorders caused by HS. Twelve rabbits were randomly assigned to one of two groups: CON (22-24°C) and HS (30°C-32°C). Both the groups were treated for 15 days. Blood and fecal samples were collected on day 15. Serum immune oxidation indices were determined using a commercial ELISA kit, and the microbiome of rabbit feces was studied using 16S rRNA gene sequencing. Non-targeted metabolomics was analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UHPC MS/MS). The findings revealed that HS significantly increased IgG and T-AOC levels in serum, whereas it decreased TNF-α and IL-10. NMDS analysis revealed a substantial difference in bacterial community composition between HS and CON groups. At the phylum level, the abundance of Firmicutes, Protobacteria, and Verrucomicrobiota was significantly higher in the HS group, whereas the abundance of Bacteriodota was reduced in the CON group. V9D2013 group, Haloplasma, Comamonas, Clostridium sensu stricto 1, Ruminiclostridium, Syntrophus Lutispora, at the genus level Syntrophorhabdus, Paeniclostridium, Clostridium sensu stricto 6, Candidatus Caldatribacterium, Spirochaeta Synergistaceae, Syner-01, [Eubacterium] xylanophilum group, Cellulosilyticum, ADurb.Bin120, and Devosia were significantly upregulated in the HS group. The metabolism of the HS group was considerably upregulated compared with the metabolism of the CON group, according to principal component analysis (PCA) and least-squares discriminant analysis (PLS-DA). HS increased the concentrations of 4-pyridoxic acid, kynurenine, 20-OH-leukotriene B4, and dopamine and decreased the concentration of pyridoxal. In the rabbit gut, these compounds primarily impact the metabolic pathways of vitamin B6, tryptophan, neutrophil activation, and prolactin. 4-Pyridoxic acid, pyridoxal, kynurenine, 20-OH-leukotriene B4, and dopamine are essential inflammatory response markers and oxidative stress.

Aqueous Extracts of Se-Enriched Auricularia auricular Exhibits Antioxidant Capacity and Attenuate Liver Damage in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

Oxidative stress triggered by hyperglycemia is thought to be a major factor in the development of liver disease during diabetes mellitus (DM). The aim of this study was to determine the antioxidant capacity of aqueous extracts of selenium-enriched Auricularia auricular (AESA) and further investigate the hepatic protection and potential mechanism of AESA in a mouse model of diabetes. An in vitro antioxidant assay confirmed that AESA exhibited better antioxidant capacity characterized by increased reducing power and scavenging capacity of free radicals, such as diphenyl picrylhydrazyl radical, hydroxyl radical, and superoxide radical. The diabetic model was induced by high-fat diet combined with a single injection of streptozotocin in C57BL/6 mice. Our results showed that AESA treatment improved diabetes-induced disorders of lipid metabolisms and alleviated liver damage in diabetic mice. Furthermore, the antioxidant enzyme activities of glutathione peroxidase and catalase in liver were increased and malondialdehyde level was decreased with AESA treatment compared with those in the DM group. In parallel, AESA significantly reduced the contents of tumor necrosis factor-alpha and interleukin-1beta in liver in comparison with the DM group. In addition, western blot results showed that the expression of receptor for advanced glycation end products (RAGE), phospho-c-Jun NH2-terminal kinase, phospho-extracellular signal-regulated kinase, and phospho-p38 kinase were remarkably decreased in AESA treatment group compared with DM group. Taken together, supplementation of AESA may effectively attenuate diabetic hepatopathology by exerting antioxidant function through the RAGE/mitogen-activated protein kinase pathway.

Aqueous extracts of se-enriched Auricularia auricular attenuates D-galactose-induced cognitive deficits, oxidative stress and neuroinflammation via suppressing RAGE/MAPK/NF-κB pathway.

Aging is a natural process that accompanied with progressive cognitive deficits and functional decline in organisms. Selenium (Se), an essential trace element, exhibits antioxidative and anti-inflammatory abilities. Here, our study aimed to investigate the protective effects of aqueous extracts of Se-enriched Auricularia auricular (AESAA) on aging mice induced by d-galactose (D-gal) and explore its potential mechanism. d-gal was administered (100 mg/kg) subcutaneously for 12 weeks to establish an aging mouse model. Morris water maze (MWM) test was conducted to assess the cognitive deficits of mice. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities and malondialdehyde (MDA) level in hippocampus were measured to evaluate oxidative stress. The contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) in hippocampus were determined by ELISA method. Further, hippocampal levels of RAGE, p-Erk, p-JNK, p-P38 and p-NF-κB were detected by western blot and the RAGE expression was confirmed by immunohistochemistry. We found that AESAA supplementation significantly decreased d-gal-induced cognitive deficits, as evidenced by better performance in the MWM test. Furthermore, AESAA treatment attenuated oxidative stress and decreased the contents of pro-inflammatory cytokines in hippocampus. Importantly, AESAA inhibited the up-regulation of RAGE, p-Erk, p-JNK, p-P38 in the hippocampus of d-gal treated mice. Moreover, the results also indicated that AESAA inhibited p-NF-κB and p-IκBα expression. In conclusion, our findings suggest that AESAA effectively decreases cognitive impairment, alleviates oxidative damage and neuroinflammation in mice through s RAGE/MAPK/NF-κB signaling pathway, which provides a potential therapy for delaying the aging process.

Comparison of breast mammography, sonography and physical examination for screening women at high risk of breast cancer in taiwan.

Recommended surveillance for screening breast cancer, which includes regular mammography and clinical breast examination, has long been established in Western countries. This strategy may be too costly and unnecessary for countries with low incidences of breast cancer. The purpose of the present study is to compare breast mammography, sonography and physical examination in screening female relatives of breast cancer index cases from the hospital, and their relative efficiency. A total of 935 women over 35 years old, who were relatives of breast cancer patients, were invited to an annual screening by means of a combination of mammography, sonography and physical examination on a single day. A biopsy was performed when any of the three investigations indicated a possibility of malignancy. A total of 21 breast cancers, including sixteen invasive cancers and 5 noninvasive cancers, were detected among the 935 high-risk women. Of the cancers, 18, including 16 invasive cancers and 3 noninvasive cancers, were detected by sonography. In contrast, only 11 invasive cancers were detected by mammography, and 7 by physical examination. There were only 14 cancers detected by a combination of mammography and physical examination. The 7 (33.3%) additional cancers were detected when sonography was added. The sensitivity of sonography was 90.4%, which was higher than mammography (52.4%) and physical examination (33.3%), or even a combination of these two modalities (66.7%). This indicates that sonography is a more accurate screening tool for breast cancer in the high-risk group. Although breast sonography has not yet been recommended as a routine screening tool for breast cancer in Western countries, it may be superior to mammography and physical examination for the screening of Taiwanese high-risk female relatives of breast cancer index cases. If it should also be considered as a routine adjunct screening modality for Taiwanese women with lower rates of breast cancer will need further study.