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This study determined the effects of dietary supplementation of rhamnolipids (RLS) on the growth performance, gut morphology, immune function, intestinal volatile fatty acid, and microflora community in Linnan yellow broilers. A total of 480 1-day-old broiler chicks were randomly assigned to groups for supplementation with one of the following for 56 d: no supplement (control), 30 mg/kg bacitracin (ANT), 500 mg/kg RLS, or 1,000 mg/kg RLS (RLS2). The RLS2 diet was found to improve the final BW and ADG on day 56. The RLS diet reduced jejunal crypt depth, increased jejunal villus length, and increased serum IgA, IgM, IgY, IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels. The RLS broilers had higher cecum concentrations of acetic acid, propionic acid, butyrate, isobutyric acid, valerate, and isovalerate. High-throughput sequencing indicated that RLS affected microbial quantity and diversity in the cecum. Bacterial richness was higher in the RLS broilers than the ANT broilers. The RLS broilers had higher relative abundances of Megasphaera hypermegale and Lachnospiraceae bacterium 19gly4 on day 28 and Clostridium spiroforme and Alistipes obesi on day 56. These results suggest that RLS supplementation improves growth performance, benefits the intestinal villus morphology, regulates host immune function, and raises intestinal volatile fatty acid content and the relative abundance of the gut microbiota in broiler chickens.

The prebiotics inulin (INU) and isomalto-oligosaccharide (IMO) influence intestinal health and immunity, but their effects on constipation are not clearly established. We evaluated the effects of INU and IMO in a rat model of diphenoxylate-induced constipation. Twenty-four male rats were divided into four groups: basal diet (Con), 40 mg kg-1 diphenoxylate (PCon), 20 g kg-1 INU and treated with 40 mg kg-1 diphenoxylate, and 20 g kg-1 IMO and treated with 40 mg kg-1 diphenoxylate. INU and IMO increased the number, weight, and water content of fecal pellets, and decreased the time to the first black stool in rats with constipation. Serum levels of the gastrointestinal motility-related hormones adrenocorticotropic hormone (ACTH), motilin (MTL), and Substance P (SP) were higher and corticosterone (CORT), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP) were lower in rats treated with prebiotics than in untreated rats. Colon tissue levels of MTL and SP were increased, and VIP and CGRP were decreased by prebiotics. Furthermore, in rats with constipation, INU and IMO increased the colonic contents of short-chain fatty acids. The relative abundance of Bacteroidetes was lower in the prebiotics groups than in the Con and PCon groups. Lactobacillus was more abundant in the INU and IMO groups than in PCon rats. Lactobacillus reuteri and Lactobacillus intestinalis were more abundant in the IMO group than in the PCon group (P < 0.01), and L. intestinalis was more abundant in the INU group than in the PCon group (P < 0.01). In summary, INU and IMO improved constipation and altered the intestinal microbiota in a rat model of constipation.

Background. Keloid has brought great trouble to people and currently has no uniformly successful treatment. It is urgent to find new targets to effectively prevent the progress of keloid. The current research mainly identifies the differentially expressed genes (DEGs) in keloid through high-throughput sequencing technology and bioinformatics analysis technology, to screen new therapeutic targets and potential biomarkers. However, due to the different samples, different control groups, and small sample sizes, the sequencing results obtained from different studies are quite different and lack reliability. It is necessary to analyze the existing datasets in a reasonable way. Methods. Datasets about keloid were filtered in Gene Expression Omnibus (GEO) and ArrayExpress databases according to the inclusion and exclusion criteria. The discovery datasets were used for summarizing significant DEGs, and the validation datasets were to validate the mRNA and miRNA expression levels. The Encyclopedia of RNA Interactomes (ENCORI) online platform was used to predict the interactions between miRNAs and their target mRNAs. Protein-protein interaction network (PPI network) analysis and functional enrichment analysis were conducted. miRNA-mRNA network was established by Cytoscape software and verified in keloid tissue ( n = 8 ) by RT-qPCR. miR-29a-3p mimic and inhibitor were transfected into keloid fibroblasts (KFs) to preliminary verify its targets, the prognostic value of which was estimated by the receiver operating characteristic (ROC) curve. Results. A total of 6 datasets involving 20 patients were included. 15 miRNAs and 12 target mRNAs were identified as potential biomarkers for keloid patients. The RT-qPCR results showed that miR-29a-3p, miR-92a-3p, and miR-143-3p were downregulated, and all their target mRNAs were upregulated in keloid tissue ( P < 0.05 ). The expression of COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2 decreased when miR-29a-3p was overexpressed but increased when miR-29a-3p was knocked down ( P < 0.05 ). And these genes had a good performance in the diagnosis of keloid, especially when using keloid nonlesional skin or normal scar tissues as controls. Conclusion. The miRNA-mRNA network, especially miR-29a-3p and its targets, may provide insights into the underlying pathogenesis of keloid and serve as potential biomarkers for keloid treatment.

GCMN is a sporadic disease with an incidence ranging from 1/20,000 to 1/500000. So far, several studies have found that GCMN is related to somatic mutations, but most of them have focused on known pathogenic genes, and transcriptome sequencing based on large datasets is relatively uncommon. At present, the use of next-generation sequencing technologies and bioinformatics platforms makes genomic information study more comprehensive and efficient. In this study, the transcriptome differences between GCMN lesions and surrounding normal skin tissues were investigated using high-throughput transcriptome sequencing, and hub genes and pathways related to pathogenesis were identified, providing a theoretical foundation for further research into the pathogenesis of GCMN.Pathological skin tissue and surrounding normal skin tissue from GCMN patients, namely the pathological group (PG) and the control group (CG), were obtained. 1. All specimens were stained with HE to ensure that the samples met the experimental requirements. 2. Ten pairs of specimens were selected for high-throughput transcriptome sequencing, and the differentially expressed genes (DEGs) between the PG and the CG were obtained. The DEGs were analyzed by clusterProfiler R software for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The function of the subnetwork was analyzed and the hub genes were identified by the STRING database and Cytoscape software. 3. The expression differences of hub genes PTGS2, EGF, and SOX10 in pathological skin tissues and normal skin tissues were verified by qRT-PCR and immunofluorescence staining.1. HE staining revealed a lot of melanocytes in the dermis and subcutaneous tissues. They were found around the hair follicles, sweat glands, sebaceous glands, and blood vessel walls, or in a specific pattern. 2. The screening threshold was set at p 0.01 and |log2fc|1, and a total of 1163 DEGs were discovered between the PG and CG, with 519 genes up-regulated and 644 genes down-regulated in the pathological tissues. According to the GO functional analysis, 29 biological processes, 18 cell compositions, and 17 molecular functions were significantly enriched, with the majority of them being related to keratinocytes and the extracellular matrix. There were 779 nodes and 2359 interactions in the protein interaction network. Using the MCODE plug-in, the network was divided into 25 functional clusters. According to ClueGO results, Cluster5 was involved in melanin biosynthesis and melanocyte proliferation. Using 11 operation methods in the Cytohubba plug-in, PTGS2, EGF, and SOX10 in Cluster5 were chosen as hub genes. 3. qRT-PCR and immunofluorescent staining revealed that compared to normal skin tissue, the expression of SOX10 was significantly up-regulated, and the expression of PTGS2 and EGF was significantly down-regulated in pathological skin tissue(P 0.001).In GCMN, keratinocytes and extracellular matrix may directly and indirectly affect melanocyte activity. PTGS2, EGF, and SOX10 are important genes and significantly differentially expressed in pathological and normal skin tissues. These findings may serve as a springboard for future research.

This study investigated the effects of dietary supplementation with Bacillus subtilis (B. subtilis) or Bacillus licheniformis (B. licheniformis) on growth performance, immunity, antioxidant capacity, short chain fatty acid (SCFA) production, and the cecal microflora in broiler chickens. In total, 360 male, 1-day-old Cobb 500 birds were randomly divided into 3 groups: the control group was fed a basal diet; the B. subtilis group was fed a basal diet supplemented with 1.5 × 109 CFU/kg B. subtilis; the B. licheniformis group was fed a basal diet supplemented with 1.5 × 109 CFU/kg B. licheniformis. Results showed that chickens supplemented with either B. subtilis or B. licheniformis had comparatively higher (P < 0.05) body weight and average daily gain, whereas no difference (P > 0.05) was observed in feed efficiency. Concentrations of serum IgA, IgY, and IgM, as well as anti-inflammatory IL-10 were significantly increased (P < 0.05), and proinflammatory IL-1β and IL-6 were significantly decreased (P < 0.05) by B. subtilis or B. licheniformis supplementation. Moreover, chickens fed with diets supplemented by either B. subtilis or B. licheniformis had greater antioxidant capacity, indicated by the notable increases (P < 0.05) in glutathione peroxidase, superoxide dismutase, and catalase, along with decrease (P < 0.05) in malondialdehyde. Compared to the control group, levels of SCFA, excluding acetic and propionic acid, in cecal content had improved (P < 0.05) by adding B. licheniformis, and significant increase (P < 0.05) in acetic and butyric acid was observed with B. subtilis supplementation. Microbial analysis showed that both B. subtilis or B. licheniformis supplementation could increase butyrate-producing bacteria such as Alistipes and Butyricicoccus, and decrease pathogenic bacteria such as the Synergistetes and Gammaproteobacteria. In summary, dietary supplemented with B. subtilis or B. licheniformis improved growth performance, immune status, and antioxidant capacity, increased SCFA production, and modulated cecal microbiota in chickens. Moreover, B. licheniformis was more effective than B. subtilis with the same supplemental amount.

Myofibroblast apoptosis is essential for normal resolution of wound repair, including cardiac infarction repair. Impaired cardiac myofibroblast (CMF) apoptosis is associated with excessive extracellular matrix (ECM) deposition, which could be responsible for pathological cardiac fibrosis. Conventionally, angiotensin II (Ang II), a soluble peptide, is implicated in fibrogenesis because it induces cardiac fibroblast (CFb) proliferation, differentiation, and collagen synthesis. However, the role of Ang II in regulation of CMF survival and apoptosis has not been fully clarified. In this report, we cultured neonatal rat CFbs, which transform into CMFs after passage 3 (6-8 days), and investigated the effects of Ang II on CMFs challenged by TNF-α combined with cycloheximide and the underlying mechanisms. Here, we show that Ang II rapidly activates MAPKs but not AKT in CMFs and confers apoptosis resistance, as evidenced by the inhibition of caspase-3 cleavage, early apoptotic cells and late apoptotic cells. This inhibitory effect of Ang II was reversed by blockade of AT1 or inactivation of ERK1/2 or RSK1 but not AT2, indicating that activation of the prosurvival AT1/ERK1/2/RSK1 signaling pathway mediates apoptosis resistance. TGF-β, a latent fibrotic factor, was found to have no relation to Ang II-induced apoptosis resistance in our study. Furthermore, Ang II-mediated apoptosis resistance, which was conferred by activation of the AT1/ERK1/2/RSK1 signaling pathway, was also confirmed in human adult ventricular cardiac myofibroblasts. Collectively, our findings suggest a novel profibrotic mechanism of Ang II in which it promotes myofibroblast resistance to apoptosis in addition to classical mechanisms, providing a potential novel therapeutic approach by targeting prosurvival signaling pathways. © 2018 IUBMB Life, 71(1):261-276, 2019.

This experiment was conducted to evaluate the effects of astragalus polysaccharides (Aps) and ginseng polysaccharide (Gps) on growth performance, liver function, immune function, TLR4 signalling pathways and intestinal barrier in weaned piglets challenged with lipopolysaccharide (LPS). In an experiment spanning 28 days, 180 weaned piglets were randomly divided into three treatment groups: basal diet (Con), basal diet supplemented with 800 mg/kg Gps (Gps) and basal diet supplemented with 800 mg/kg Aps (Aps). At the end of the experiment, 12 piglets of each group were selected; half (n = 6) were intraperitoneally injected with LPS and half with normal saline. Dietary supplementation with Aps and Gps significantly increased (p < .05) the average daily gain and feed conversion rate. Lipopolysaccharide challenge increased (p < .05) expression of serum urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-1β (IL-1β) and tumour inflammatory factor-α (TNF-α), but decreased (p < .05) serum superoxide dismutase (SOD) level, total antioxidant capacity (T-AOC) and immunoglobulin A (IgA) expression. Lipopolysaccharide-challenged piglets fed with Aps or Gps had lower (p < .05) BUN, ALT, AST, IL-1β and TNF-α levels and greater (p < .05) SOD, T-AOC and IgA levels. Lipopolysaccharide challenge increased (p < .05) the expression of TLR4, MyD88 and NF-κB, and LPS-challenged piglets fed diets supplemented with Aps or Gps increased TLR4 and MyD88 and decreased NF-κB expression. Lipopolysaccharide challenge reduced (p < .05) the jejunal villus height, and piglets fed with Aps or Gps had increased (p < .05) jejunal villus height. Supplementation with Aps or Gps enhanced the expression of occludin and claudin in challenged or unchallenged piglets. In conclusion, dietary supplementation with Aps or Gps enhanced piglet growth performance, alleviated liver dysfunction and reduced immunological stress caused by LPS, as well as increased the intestinal barrier function.

Antibiotic resistance is a major issue in animal industries and antibiotic-free alternatives are needed to treat infectious diseases and improve performance of pigs. Plant extracts have been suggested as a potential solution. The present study was conducted to investigate the effects of Astragalus polysaccharides (Aps) and ginseng polysaccharide (Gps) on growth performance, intestinal morphology, immune function, volatile fatty acids (VFAs), and microfloral community in weaned piglets. A total of 180 weaned piglets were randomly divided into three treatment groups during a 28-days feeding experiment, including a basal diet (Con), basal diet supplemented with 800 mg/kg Aps (Aps), and basal diet supplemented with 800 mg/kg Gps (Gps). Results showed that both Aps and Gps increased body weight, average daily gain and feed conversion rate, and reduced the rate of diarrhea. Gps also decreased aspartate aminotransferase compared to the Con piglets after 14 days. No significant effects on alanine aminotransferase were observed. Both Aps and Gps piglets exhibited higher serum immunoglobulin M levels after 14 and 28 days, and also decreased jejunal crypt depth, increased jejunal villus length and villus height/crypt depth ratio, and increased expression of toll-like receptor 4, myeloid differentiation primary response 88, nuclear factor-kappa B proteins in the jejunum. Aps and Gps piglets also had higher concentrations of acetic acid, isobutyric acid, and butyrate in their colon. Data of high-throughput sequencing revealed that Aps and Gps affected bacterial quantity and diversity in the colon. Species richness and evenness were higher in both Aps and Gps piglets than the control piglets. Aps and Gps piglets also had a higher relative abundance of Lachnospiraceae and Anaerostipes, and the Aps piglets had a higher relative abundance of Lactobacillus gasseri and L. amylovorus. Therefore, dietary supplementation with Aps and Gps could be beneficial for optimizing the performance of industry pigs and reducing dependence on antibiotics. Furthermore, Plant polysaccharides play a great role in promoting the sustainable development of animal husbandry.