Exploring PLGA-OH-CATH30 Microspheres for Oral Therapy of Escherichia coli-Induced Enteritis.

Antibiotic therapy effectively addresses Escherichia coli-induced enteric diseases, but its excessive utilization results in microbial imbalance and heightened resistance. This study evaluates the therapeutic efficacy of orally administered poly (lactic-co-glycolic acid) (PLGA)-loaded antimicrobial peptide OH-CATH30 microspheres in murine bacterial enteritis. Mice were categorized into the healthy control group (CG), untreated model group (MG), OH-CATH30 treatment group (OC), PLGA-OH-CATH30 treatment group (POC), and gentamicin sulfate treatment group (GS). Except for the control group, all other experimental groups underwent Escherichia coli-induced enteritis, followed by a 5-day treatment period. The evaluation encompassed clinical symptoms, intestinal morphology, blood parameters, inflammatory response, and gut microbiota. PLGA-OH-CATH30 microspheres significantly alleviated weight loss and intestinal damage while also reducing the infection-induced increase in spleen index. Furthermore, these microspheres normalized white blood cell count and neutrophil ratio, suppressed inflammatory factors (IL-1ß, IL-6, and TNF-α), and elevated the anti-inflammatory factor IL-10. Analysis of 16S rRNA sequencing results demonstrated that microsphere treatment increased the abundance of beneficial bacteria, including Phocaeicola vulgatus, in the intestinal tract while concurrently decreasing the abundance of pathogenic bacteria, such as Escherichia. In conclusion, PLGA-OH-CATH30 microspheres have the potential to ameliorate intestinal damage and modulate the intestinal microbiota, making them a promising alternative to antibiotics for treating enteric diseases induced by Escherichia coli.

Vaccines for African swine fever: an update.

African swine fever (ASF) is a fatal infectious disease of swine caused by the African swine fever virus (ASFV). Currently, the disease is listed as a legally notifiable disease that must be reported to the World Organization for Animal Health (WOAH). The economic losses to the global pig industry have been insurmountable since the outbreak of ASF. Control and eradication of ASF are very critical during the current pandemic. Vaccination is the optimal strategy to prevent and control the ASF epidemic, but since inactivated ASFV vaccines have poor immune protection and there aren't enough cell lines for efficient in vitro ASFV replication, an ASF vaccine with high immunoprotective potential still remains to be explored. Knowledge of the course of disease evolution, the way of virus transmission, and the breakthrough point of vaccine design will facilitate the development of an ASF vaccine. In this review, the paper aims to highlight the recent advances and breakthroughs in the epidemic and transmission of ASF, virus mutation, and the development of vaccines in recent years, focusing on future directions and trends.

Comparative transcriptomic analysis of PK15 cells infected with a PRV variant and the Bartha-K/61 vaccine strain.

Introduction: Pseudorabies virus (PRV) is a herpesvirus that can infect domestic animals, such as pigs, cattle and sheep, and cause fever, itching (except pigs), and encephalomyelitis. In particular, the emergence of PRV variants in 2011 have resulted in serious economic losses to the Chinese pig industry. However, the signaling pathways mediated by PRV variants and their related mechanisms are not fully understood. Methods: Here, we performed RNA-seq to compare the gene expression profiling between PRV virulent SD2017-infected PK15 cells and Bartha-K/61-infected PK15 cells. Results: The results showed that 5,030 genes had significantly different expression levels, with 2,239 upregulated and 2,791 downregulated. GO enrichment analysis showed that SD2017 significantly up-regulated differentially expressed genes (DEGs) were mainly enriched in the binding of cell cycle, protein and chromatin, while down-regulated DEGs were mainly enriched in ribosomes. KEGG enrichment analysis revealed that the pathways most enriched for upregulated DEGs were pathways in cancer, cell cycle, microRNAs in cancer, mTOR signaling pathway and autophagy-animal. The most down-regulated pathways of DEGs enrichment were ribosome, oxidative phosphorylation, and thermogenesis. These KEGG pathways were involved in cell cycle, signal transduction, autophagy, and virus-host cell interactions. Discussion: Our study provides a general overview of host cell responses to PRV virulent infection and lays a foundation for further study of the infection mechanism of PRV variant strain.

LncRNA AK131850 is downregulated in thoracic aortic aneurysm and negatively affects the levels of TGF-ß1 in aortic smooth muscle cells.

This study aimed to investigate the role of lncRNA AK131850 in thoracic aortic aneurysm (TAA). We found that AK131850 was downregulated, while TGF-ß1 was upregulated in aortic media specimen of thoracic aortic aneurysm (TAA) patients. In addition, AK131850 and TGF-ß1 inversely correlated. Altered expression levels of AK131850 and TGF-ß1 distinguished TAA patients from healthy controls. In human aortic smooth muscle cells (HAOSMC), AK131850 overexpression led to downregulated, while AK131850 siRNA silencing led to upregulated TGF-ß1. AK131850 overexpression resulted in promoted, while siRNA silencing led to inhibited proliferation of HAOSMC. Therefore, AK131850 is downregulated in thoracic aortic aneurysm and negatively affects the levels of TGF-ß1 in aortic smooth muscle cells.

Orally administered recombinant Lactobacillus expressing African swine fever virus antigens that induced immunity responses.

African swine fever (ASF) is a highly contagious, acute, febrile disease caused by the African swine fever virus (ASFV), with morbidity and mortality rates approaching 100% in domestic and wild swine, resulting in massive economic losses to the pig industry worldwide. This study aimed to express the p30, p54, and p72 proteins encoded by ASFV in vitro using the Lactobacillus lactis (L. lactis) expression system. Here, six new functional recombinant L. lactis were constructed, and the expression of the p30 protein, p54 protein, p72 protein, p30-LTB (heat-labile enterotoxin B, LTB) fusion protein, p54-LTB fusion protein, and the p72-LTB fusion protein was successfully detected by Western blot analysis. Following oral immunization of rabbits with recombinant L. lactis, serum IgG, intestinal mucosal sIgA, cytokines (IL-4 and INF-γ), and splenocyte viability were higher than in the control group via ELISA. Notably, without the LTB adjuvant group, humoral and Th1 cellular immunity were promoted, whereas, with the LTB adjuvant group, local mucosal immunity, humoral immunity, and Th2 cellular immunity were promoted, providing new insights into the design and development of an ASFV subunit vaccine.

Effects of Enteromorpha polysaccharide dietary addition on the diversity and relative abundance of ileum flora in laying hens.

This experiment explored the effects of different levels of Enteromorpha polysaccharide dietary addition on the intestinal flora structure in laying hens. A total of 300 Hy-line brown laying hens aged 280 days old were selected according to the principle of equal weight and egg production rate. Group 1 was the blank control group fed with basic diet, Group 2 was the antibiotic control group supplemented with bacitracin zinc (0.005%) and basic diet, and Groups 3-5 were the experimental groups that received 0.1%, 0.2%, and 0.4% Enteromorpha polysaccharides in their diets, respectively. Four replicates per group and 15 repeats per replicate were prepared. The pretrial period was 10 days, and the normal trial period was 42 days. The ileum contents of laying hens were collected aseptically toward the end of the test to detect the diversity and relative abundance of the flora. Results were as follows. (1) Bacterial abundance (ACE and Chao1) and diversity (Simpson and Shannon) indexes were not significantly different between the control and test groups (P > 0.05). (2) Compared with that in group 1, the relative abundance of Firmicutes in groups 4 and 5 significantly increased by 14.13% (P < 0.05) and 13.70% (P < 0.05), respectively. The relative abundance of Bacilli in group 4 was significantly increased by 11.94% (P < 0.05) and 12.86% (P < 0.05) compared with those in groups 1 and 3, respectively. The relative abundance of Lactobacillales in group 4 was significantly increased by 27.02% (P < 0.05) compared with that in group 1. The relative abundance of Lactobacillaceae in group 4 was significantly increased by 22.92% (P < 0.05) and 11.4% (P < 0.05) compared with those in groups 1 and 3, respectively. The relative abundance of Lactobacillus in groups 4 and 5 was increased by 19.75% (P < 0.05) and 18.54% (P < 0.05), respectively. CONCLUSION: The dietary addition of 0.2% Enteromorpha polysaccharides can remarkably increase the relative abundance of Firmicutes phylum, Bacilli class, Lactobacillales order, Lactobacillaceae family, and Lactobacillus genus in the ileum of laying hens. This effect was equivalent to the action of bacitracin zinc and had no substantial influence on the diversity of ileum flora.

Characterization of a Novel N-Acylhomoserine Lactonase RmmL from Ruegeria mobilis YJ3.

Gram-negative bacteria utilize N-acylhomoserine lactones (AHLs) as quorum sensing (QS) signaling molecules for intercellular communication. Cell-to-cell communication depends on cell population density, and AHL-dependent QS is related to the production of multiple genes including virulence factors. Quorum quenching (QQ), signal inactivation by enzymatic degradation, is a potential strategy for attenuating QS regulated bacterial infections. Both Gram-positive and -negative bacteria have QQ enzymes that can degrade AHLs. In our previous study, strain Ruegeria mobilis YJ3, isolated from healthy shrimp, showed strong AHLs degradative activity. In the current study, an AHL lactonase (designated RmmL) was cloned and characterized from Ruegeria mobilis YJ3. Amino acid sequence analysis showed that RmmL has a conserved "HXHXDH" motif and clusters together with lactonase AidC that belongs to the metallo-ß-lactamase superfamily. Recombinant RmmL could degrade either short- or long-chain AHLs in vitro. High-performance liquid chromatography analysis indicated that RmmL works as an AHL lactonase catalyzing AHL ring-opening by hydrolyzing lactones. Furthermore, RmmL can reduce the production of pyocyanin by Pseudomonas aeruginosa PAO1, while for the violacein and the extracellular protease activities by Chromobacterium violaceum CV026 and Vibrio anguillarum VIB72, no significant reduction was observed. This study suggests that RmmL might be used as a therapeutic agent in aquaculture.

IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice.

BACKGROUND AND OBJECTIVE: Interleukin 6 (IL-6) has been identified as a key mediator in inflammation, immune responses and glucose metabolism. In this study, we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a mouse model of type 2 diabetes mellitus. METHODS: Twelve week old male db/db mice were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and insulin resistance were assessed. RESULTS: Db/db mice treated with Tocilizumab exhibited reduced proteinuria and glomerular mesangial matrix accumulation compared to db/db + IgG controls. Additionally, Tocilizumab suppressed inflammatory response, oxidative stress and the IL-6 signaling pathway in the diabetic kidneys. It is noteworthy that blockade of IL-6 receptor blunted the activation of NLRP3 inflammasome partly through inhibition of IL-17A. Furthermore, insulin resistance assessed by glucose tolerance test, was ameliorated by Tocilizumab treatment. CONCLUSIONS: The protective effects of an IL-6 receptor blockade against diabetic renal injury may be due to decreased insulin resistance and inhibition of the inflammasome.

Paraphaeobacter pallidus gen. nov., sp. nov., isolated from seawater.

A Gram-stain-negative, aerobic, rod-shaped bacterium with a single polar flagellum, designated strain DCSW07T, was isolated from the surface water of the Bohai Sea, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain DCSW07T shared highest similarity (96.97 %) with Phaeobacter gallaeciensis DSM 26640T, formed a lineage within the family Rhodobacteraceae and was distinct from the most closely related genera Phaeobacter and Pseudooceanicola (96.6-96.8 and 95.8-96.2 % 16S rRNA gene sequence similarity, respectively). Optimal growth occurred in the presence of 6 % (w/v) NaCl, at pH 6.0 and at 28 °C. Strain DCSW07T contained phosphatidylcholine, phosphatidylethanolamine, an unidentified phospholipid and two unidentified polar lipids as the major polar lipids, and C18 : 1ω7c as the main fatty acid (>10 % of the total). The DNA G+C content of strain DCSW07T was 64.8 mol%. On the basis of this polyphasic study, strain DCSW07T is considered to represent a novel species of a new genus in the Roseobacter clade of the family Rhodobacteraceae, for which the name Paraphaeobacter pallidus gen. nov., sp. nov. is proposed. The type strain of Paraphaeobacter pallidus is DCSW07T (=KCTC 52369T=MCCC 1K03197T=JCM 31458T=CGMCC 1.15762T).

The importance of N-glycosylation on ß3 integrin ligand binding and conformational regulation.

N-glycosylations can regulate the adhesive function of integrins. Great variations in both the number and distribution of N-glycosylation sites are found in the 18 α and 8 ß integrin subunits. Crystal structures of αIIbß3 and αVß3 have resolved the precise structural location of each N-glycan site, but the structural consequences of individual N-glycan site on integrin activation remain unclear. By site-directed mutagenesis and structure-guided analyses, we dissected the function of individual N-glycan sites in ß3 integrin activation. We found that the N-glycan site, ß3-N320 at the headpiece and leg domain interface positively regulates αIIbß3 but not αVß3 activation. The ß3-N559 N-glycan at the ß3-I-EGF3 and αIIb-calf-1 domain interface, and the ß3-N654 N-glycan at the ß3-ß-tail and αIIb-calf-2 domain interface positively regulate the activation of both αIIbß3 and αVß3 integrins. In contrast, removal of the ß3-N371 N-glycan near the ß3 hybrid and I-EGF3 interface, or the ß3-N452 N-glycan at the I-EGF1 domain rendered ß3 integrin more active than the wild type. We identified one unique N-glycan at the ßI domain of ß1 subunit that negatively regulates α5ß1 activation. Our study suggests that the bulky N-glycans influence the large-scale conformational rearrangement by potentially stabilizing or destabilizing the domain interfaces of integrin.