Putative role of STING-mitochondria associated membrane crosstalk in immunity.

Stimulator of interferon genes (STING) has emerged as a key regulator of innate immunity, recognizing intracellular exogenous and endogenous DNA. Recent findings reveal that STING has multiple cell-specific immune functions in various pathological settings, including pathogenic infections, cancer, and autoimmune diseases. Here, we hypothesize that this unique location of STING in the mitochondria-associated membrane (MAM) might lead to the specificity of the cellular functions of STING mediated by mitochondria-ER communication. This new insight suggests that STING on the MAM might act as a hub that translates multiple cues on MAM into distinct cellular responses. This innovative view of STING biology might impart insights for future putative treatments in cancer and immune diseases that have been attributed to STING dysfunction.

Combating bacterial infections with host defense peptides: Shifting focus from bacteria to host immunity.

The increasing prevalence of multidrug-resistant bacterial infections necessitates the exploration of novel paradigms for anti-infective therapy. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), have garnered extensive recognition as immunomodulatory molecules that leverage natural host mechanisms to enhance therapeutic benefits. The unique immune mechanism exhibited by certain HDPs that involves self-assembly into supramolecular nanonets capable of inducing bacterial agglutination and entrapping is significantly important. This process effectively prevents microbial invasion and subsequent dissemination and significantly mitigates selective pressure for the evolution of microbial resistance, highlighting the potential of HDP-based antimicrobial therapy. Recent advancements in this field have focused on developing bio-responsive materials in the form of supramolecular nanonets. A comprehensive overview of the immunomodulatory and bacteria-agglutinating activities of HDPs, along with a discussion on optimization strategies for synthetic derivatives, is presented in this article. These optimized derivatives exhibit improved biological properties and therapeutic potential, making them suitable for future clinical applications as effective anti-infective therapeutics.

Aromatic Amino Acids Promote Lipid Metabolism Disorders by Increasing Hepatic Bile Acid Synthesis.

BACKGROUND: Obesity is a progressive metabolic disease that begins with lipid metabolism disorders. Aromatic amino acids (AAAs), including tryptophan, phenylalanine, and tyrosine, have diverse biological activities as nutrients. However, the underlying mechanisms by which AAAs affect lipid metabolism are unclear. OBJECTIVES: This study was designed to investigate the possible roles and underlying molecular mechanisms of AAA in the pathogenesis of lipid metabolism disorders. METHODS: We added an AAA mixture to the high-fat diet (HFD) of mice. Glucose tolerance test was recorded. Protein expression of hepatic bile acid (BA) synthase and mRNA expression of BA metabolism-related genes were determined. Hepatic BA profiles and gut microbial were also determined in mice. RESULTS: The results showed that AAA significantly increased body weight and white adipose tissue, aggravated liver injury, impaired glucose tolerance and intestinal integrity, and significantly increased hepatic BA synthesis by inhibiting intestinal farnesoid X receptor (FXR). Moreover, AAA increased the content of total BA in the liver and altered the hepatic BA profile, with elevated levels of lithocholic acid, glycochenodeoxycholic acid, and glycoursodeoxycholic acid. AAA markedly increased the levels of proteins involved in BA synthesis (cholesterol 7α-hydroxylase and oxysterol 7α-hydroxylase) and inhibited the intestinal FXR. Gut microbial composition also changed, reducing the abundance of some beneficial bacteria, such as Parvibacter and Lactobacillus. CONCLUSIONS: Under HFD conditions, AAAs stimulate BA synthesis in both the classical and alternative pathways, leading to aggravation of liver injury and fat deposition. Excessive intake of AAA disrupts BA metabolism and contributes to the development of lipid metabolism disorders, suggesting that AAA may be a causative agent of lipid metabolism disorders.

Oleanolic acid attenuates hydrogen peroxide-induced apoptosis of IPEC-J2 cells through suppressing c-Jun and MAPK pathway.

Oleanolic acid (OA) is a natural triterpenoid with therapeutic potential for a multitude of diseases. However, the precise mechanism by which OA influences stress-induced apoptosis of intestinal epithelial cells remains elusive. Therefore, the effect of OA on intestinal diseases under stressful conditions and its possible mechanisms have been investigated. In a hydrogen peroxide (H2 O2 )-induced oxidative stress model, OA attenuated H2 O2 -induced apoptosis in a concentration-dependent manner. To investigate the underlying mechanisms, the gene expression profile of OA on IPEC-J2 cells was analyzed using an RNA sequencing system. Results from gene ontology and Kyoto encyclopedia of genes and genomes analysis confirmed that OA may mitigate the cytotoxic effects of H2 O2 by downregulating gene expression through the MAPK signaling pathway. Furthermore, Quantitative real-time polymerase chain reaction results validated the differentially expressed genes data. Western blot analysis further demonstrated that OA effectively suppressed the expression level of c-Jun protein induced by H2 O2 in IPEC-J2 cells. Collectively, our results indicate that OA pretreatment significantly attenuated H2 O2 -induced apoptosis in intestinal epithelial cells through suppressing c-Jun and MAPK pathway.

Dietary pterostilbene exerts potential protective effects by regulating lipid metabolism and enhancing antioxidant capacity on liver in broilers.

Intensive breeding of broilers met the increasing demands of human for broiler products, but it raised their increased susceptibility to various stressors resulting in the disorder of lipid metabolism. Pterostilbene, the methoxylated analogue of resveratrol, exhibits astonishing functions of antioxidant, anti-inflammatory and glycolipid regulatory. The study aimed to elucidate the protective effects of pterostilbene on broiler liver and to explore the potential mechanisms. A total of 480 one-day-old male Arbor Acres (AA) broilers were randomly divided into four groups: the control group (basal diet) and pterostilbene groups (PT200, PT400, and PT600 feeding with basal diet containing 200, 400 and 600 mg/kg pterostilbene, respectively). The results showed that the dietary pterostilbene supplementation significantly improved the ADG of broilers. Dietary pterostilbene supplementation regulated the expression levels of the genes Sirt1 and AMPK and the downstream genes related to lipid metabolism to protect liver function and reduce lipid accumulation in broilers. Dietary pterostilbene supplementation upregulated the expression levels of the Nrf2 gene and its downstream antioxidant genes (SOD, CAT, HO-1, NQO-1, GPX) and phase II detoxification enzyme-related genes (GST, GCLM, GCLC). Collectively, pterostilbene was confirmed the positive effects as a feed additive on lipid metabolism and antioxidant via regulating Sirt1/AMPK and Nrf2 signalling pathways in broilers.

Cannabidiol ameliorates inflammatory response partly by AGE-RAGE pathway in diabetic mice.

Cannabidiol (CBD), the most abundant nonpsychoactive constituent of Cannabis sativa plant, is a promising potential pharmacotherapy for the treatment of diabetes and associated comorbidities. Previous studies have shown the potential of CBD to prevent diabetes in mice, the precise mechanisms of action remain unclear. The purpose of this study was to explore the mechanism of CBD alleviating hyperglycemia. The results demonstrated that CBD reduced blood glucose of STZ-induced diabetic mice without causing hypoglycemia. To elucidate the possible mechanisms of CBD effect, RNA-seq analysis was performed on high glucose-induced human mesangial cells (HMCs). By cluster analysis of differential genes, the results showed that advanced glycation end products-receptor of advanced glycation endproducts (AGE-RAGE) pathway-related genes CCL2 and interleukin-1ß (IL-1ß) play an important role in the biological of CBD. The expression of CCL2 and IL-1ß were significantly increased in HMCs. Whereas, treatment with CBD decreased the expression of CCL2 and IL-1ß. In addition, CBD significantly reduced AGE-RAGE levels in high glucose-induced HMCs. Similar results were confirmed in diabetic mice. In conclusion, we discovered for the first time that CBD ameliorates hyperglycemia partly through AGE-RAGE mediated CCL2/IL-1ß pathway.

Anti-Proteolytic Peptide R7I Protects the Intestinal Barrier and Alleviates Fatty Acid Malabsorption in Salmonella typhimurium-Infected Mice.

With a wide range of hosts, environmental adaptation, and antibiotic resistance, Salmonella typhimurium is one of the most common causes of food poisoning in the world. Infection with Salmonella typhimurium not only results in intestinal inflammation but also damages the intestinal barrier and interferes with the host's ability to absorb nutrients. It is imperative to find alternatives to antibiotics for eradicating bacteria, reducing intestinal damage, and reestablishing nutrient absorption, especially given that antibiotics are currently prohibited. This research aims to understand the protective role of anti-proteolytic peptide R7I on the gut in the setting of Salmonella typhimurium infection and its impact on nutritional absorption, maybe offering an alternative to antibiotics for bacterial killing. The findings demonstrated that R7I reduced the production of inflammatory factors, including IL-6, TNF-α, and L-1ß in the jejunum and decreased the expression of genes like TLR4 and NF-κB in the jejunum (p < 0.05). R7I enhanced antioxidant capacity and preserved the antioxidant/pro-oxidant balance in the jejunum (p < 0.05). R7I also normalized intestinal shape and restored tight junction protein expression. Fatty acid binding protein 2 (FABP2) and fatty acid transport protein 4 (FATP4) expression in the jejunum was restored by R7I. In addition, serum-free fatty acids and lipid metabolites were significantly higher in the R7I group than in the control group (p < 0.05). Overall, the anti-enzyme peptide R7I maintained the healthy state of the intestine and alleviated the abnormal fatty acid absorption caused by bacterial infection.

Effects of sweet potato vine silage supplementation on meat quality, antioxidant capacity and immune function in finishing pigs.

Sweet potato vine, the byproduct of sweet potato, has a high nutritional value. Silage is an effective solution for nutrient preservation. This article explored the effects of sweet potato vine silage (SPVS) supplementation on meat quality, antioxidant capacity and immune function in finishing pigs. One hundred and eighty finishing pigs (Berkshire × Licha Black) with a body weight of 74.54 ± 3.32 kg were randomly divided into three groups. The three groups were separately fed basal diet (Ctrl), Ctrl supplemented with 2.5% SPVS (LSPVS) or 5% SPVS (HSPVS) on a dry matter basis. Results showed that the eye muscle area in the LSPVS group was significantly increased. The carcass weight in the HSPVS was significantly reduced compared with Ctrl. For the meat quality, only cooking loss in both HSPVS and LSPVS was reduced while other indexes had no significant differences. For the antioxidant capacity, the hepatic level of glutathione (GSH) peroxidase (GSH-PX) was significantly upregulated in LSPVS but downregulated in HSPVS. In the serum, HSPVS decreased GSH level and increased GSH-PX level. HSPVS significantly reduced hepatic interleukin-1ß (IL-1ß) levels and LSPVS significantly reduced IL-12 levels and increased IL-8 and IL-6 levels. Moreover, HSPVS and LSPVS promoted the secretion of immunoglobulin M (IgM) and IgG in the serum. Our data showed that low-dose SPVS supplementation improved carcass traits and high-dose SPVS supplementation increased immune function in finishing pigs, which provides a new alternative to improve animal health.

Lycopene Affects Intestinal Barrier Function and the Gut Microbiota in Weaned Piglets via Antioxidant Signaling Regulation.

BACKGROUND: In pig production, early and abrupt weaning frequently causes weaning stress, which manifests as oxidative damage, barrier disruption, and digestion and absorption capacity declines. Lycopene exhibits beneficial antioxidant capacity in both humans and other animal models. OBJECTIVES: The present study aimed to investigate the effects of lycopene supplementation on early weaning stress in piglets and the underlying mechanisms by examining the oxidative stress state, gut intestinal barrier function, and the gut microbiota. METHODS: Twenty-four 21-day-old weaned piglets [Duroc × (Landrace × Yorkshire); castrated males; 5.48 ± 0.10 kg initial body weight] were randomly assigned to 2 treatments. The piglets were fed a basal diet (control treatment) or a basal diet supplemented with 50 mg/kg lycopene (lycopene treatment) for 28 days. The serum lipid levels, serum and jejunum enzyme activities, jejunum morphology, mRNA and protein expression, and gut microbiota were determined. RESULTS: Compared with the control treatment, lycopene supplementation increased the serum catalase activity (P = 0.042; 62.0%); serum total cholesterol concentration (P = 0.020; 14.1%); and jejunum superoxide dismutase activity (P = 0.032; 21.4%), whereas it decreased serum (P = 0.039, 23.0%) and jejunum (P = 0.047; 20.9%) hydrogen peroxide concentrations. Additionally, lycopene increased the mRNA and protein expression of NFE2-like bZIP transcription factor 2 (214.0% and 102.4%, respectively) and CD36 (100.8% and 145.2%, respectively) in the jejunum, whereas it decreased the mRNA and protein expression of Kelch-like ECH-associated protein 1 (55.6% and 39.8%, respectively ). Lycopene also improved jejunal morphology, increasing the villus height (P = 0.018; 27.5%) and villus:crypt ratio (P < 0.001; 57.9%). Furthermore, it increased the abundances of potentially beneficial bacterial groups, including Phascolarctobacterium and Parasutterella, and decreased those of potentially pathogenic bacterial groups, including Treponema_2 and Prevotellaceae_unclassified. CONCLUSIONS: Lycopene supplementation strengthens the intestinal barrier function and improves the gut microbiota in weaned piglets by regulating intestinal antioxidant signaling.

Dihydroartemisinin alleviates deoxynivalenol induced liver apoptosis and inflammation in piglets.

Deoxynivalenol (DON) is one of the mycotoxins that contaminate cereals and feed, thereby endangering human and animal health. Dihydroartemisinin (DHA), a derivative of artemisinin, has anti-inflammatory and antioxidant functions in addition to anti-malaria and anti-cancer. The purpose of this study was to investigate the effects of DHA on alleviating liver apoptosis and inflammation induced by DON in piglets. The experimental design followed a 2 (normal diet and DON-contaminated diet) × 2 (with and without supplementation of DHA) factorial arrangement. 36 weaned piglets were subjected to a 21-day experiment. Results showed that DON increased ALT activity, the levels of TNF-α, IL-1ß and IL-2, and reduced the levels of total protein (TP) and albumin (ALB) in the serum. However, DHA decreased the levels of TNF-α, IL-1ß and IL-2, and increased the levels of TP and ALB. Also, DON decreased glutathione (GSH) content and catalase (CAT) activity, and increased methane dicarboxylic aldehyde (MDA) content. But GSH content was increased by DHA. In addition, DHA decreased DON-induced increase in apoptosis rate of hepatocytes. Furthermore, DON activated death receptor pathway to promote apoptosis by up-regulating the protein expression of FasL and caspase-3, and the mRNA expression of FasL, TNFR1, caspase-8, Bid, Bax, CYC and caspase-3. However, DHA reduced caspase-3 protein expression, as well as the mRNA expression of FADD, Bid, Bax, CYC and caspase-3. Besides, DON also activated TNF/NF-κB pathway to induce an inflammatory response by up-regulating TNF-α protein expression, and the mRNA expression of TNFR1, RIP1, IKKß, IκBα, IL-1ß and IL-8. Nevertheless, DHA reduced the mRNA expression of RIP1, IκBα, NF-κB, IL-1ß and IL-6, and the protein expression of TNF-α and NF-κB. In conclusion, DHA improved DON-induced negative effects on serum biochemical parameters and inflammatory cytokine levels, hepatic antioxidant capacity, hepatic apoptosis and inflammation.

Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells.

Zearalenone (ZEN) is a widespread contaminant of cereals and agricultural products which causes food safety issues. Ingesting food or feed contaminated with ZEN can disrupt the intestinal epithelial barrier function. The RhoA/ROCK signaling pathway plays a key role in regulating the epithelial barrier function, but studies on such roles have rarely focused on the intestine. The aim of this experiment was to investigate the exact mechanism of ZEN-induced intestinal barrier damage and whether the RhoA/ROCK signaling pathway is involved. The results showed that ZEN significantly induced alkaline phosphatase (AP) activity and FITC-dextran (4 kDa) passage across the epithelial barrier, which significantly reduced the transepithelial resistance (TEER). Meanwhile, ZEN could induce the significantly down-regulated mRNA expression of tight junction proteins (occludin, claudin-1, ZO-1, and claudin-3) and redistribution of ZO-1 immunofluorescence. Further studies demonstrated that ZEN exposure activated the RhoA/ROCK signaling pathway, significantly up-regulated the mRNA expression of ROCK1, the main effector of the signaling pathway, the protein expression of phosphorylated myosin light chain (MLC) and myosin light chain kinase (MLCK), and relatively increased the activity of ATP in cells, simultaneously remodeling the cytoskeleton (F-actin). Overall, our study indicated that ZEN induced intestinal barrier dysfunction by activating the RhoA/ROCK signaling pathway.

Oleanolic acid reshapes the gut microbiota and alters immune-related gene expression of intestinal epithelial cells.

BACKGROUND: Oleanolic acid (OA) is a pentacyclic triterpenoid compound that is present at high levels in olive oil and has several promising pharmacological effects, such as liver protection and anti-inflammatory, antioxidant, and anticancer effects. The purpose of the present study was to assess whether OA treatment affects gut health compared to a control condition, including gut microbiota and intestinal epithelial immunity. RESULTS: Illumina MiSeq sequencing (16S rRNA gene) was used to investigate the effect of OA on the microbial community of the intestinal tract, while Illumina HiSeq (RNA-seq) technology was used to investigate the regulatory effect of OA on gene expression in intestinal epithelial cells, which allowed for a comprehensive analysis of the effects of OA on intestinal health. The results showed that the consumption of OA initially controlled weight gain in mice and altered the composition of the gut microbiota. At the phylum level, OA significantly increased the relative abundances of cecum Firmicutes but decreased the abundance of Actinobacteria, and at the genus level it increased the relative abundance of potentially beneficial bacteria such as Oscillibacter and Ruminiclostridium 9. Oleanolic acid treatment also altered the expression of 12 genes involved in the Kyoto Encyclopedia of Genes and Genomes（KEGG）pathways of complement and coagulation cascades, hematopoietic cell lineage, and leukocyte transendothelial migration in intestinal epithelial cells to improve gut immunity. CONCLUSION: Intake of OA can contribute beneficial effects by optimizing gut microbiota and altering the immune function of intestinal epithelial cells, potentially to improve intestinal health status. © 2021 Society of Chemical Industry.

Aquaporin: targets for dietary nutrients to regulate intestinal health.

Aquaporins (AQP) are a class of water channel membrane proteins that are widely expressed in the gut. The biological functions of aquaporins, which regulate the absorption and secretion of water molecules and small solutes, maintain the stable state of the intestine, regulate cell proliferation and migration, participate in the process of intestinal inflammation, and mediate tumorigenesis, demonstrate the physiological significance of these channels in intestinal health. The pathology of many intestinal diseases is associated with changes in the location and expression of aquaporins, such as intestinal infection, which can change the expression and distribution of AQPs in intestinal tissues/cells by affecting cytokines and chemokines. This can lead to various intestinal diseases such as diarrhoea, which also suggests the importance of aquaporins in the prevention and treatment of intestinal diseases. This review summarizes the relationship between aquaporins and intestinal physiology and diseases and focuses on drugs (such as plant extracts) or diets that can regulate intestinal health by regulating aquaporins. It provides a basis for establishing aquaporins as biomarkers and therapeutic targets for intestinal health.

Dietary resveratrol alleviated lipopolysaccharide-induced ileitis through Nrf2 and NF-κB signalling pathways in ducks (Anas platyrhynchos).

Gram-negative bacteria contamination of feed can occur at all the stage of feed production, storage, transportation and utilization. Lipopolysaccharide (LPS) is a major toxic metabolite of Gram-negative bacteria. The aim of this study was to explore the effect of dietary resveratrol on the duck ileitis caused by LPS and its optimum addition level in diet. The results showed that LPS-induced duck ileitis with the destruction of intestinal structure, oxidative stress, mitochondrial dysfunction, inflammatory response and permeability alteration. Dietary resveratrol alleviated LPS-induced intestinal dysfunction and the increase of intestinal permeability by linearly increasing mRNA levels of tight junction protein genes (Claudin-1, Occludin-1, ZO-1) (p < 0.05) and protein expression of Claudin-1 (p < 0.01). In addition, dietary resveratrol improved the antioxidant capacity of duck ileum by reducing the production of MDA and increasing the activity of T-SOD (p < 0.01) and CAT. Lipopolysaccharide increased Keap1 at mRNA and protein level (p < 0.01) and decreased the protein level of Nrf2 (p < 0.05). Dietary resveratrol significantly downregulated expression of Keap1 and upregulated expression of Nrf2 in duck (p < 0.05). Dietary resveratrol suppressed the TLR4/NF-κB signalling pathway and the expression of its downstream genes including IKK, TXNIP, NLRP3, Caspase-1, IL-6 and IL-18. Meanwhile, the levels of inflammatory cytokines (IL-6, IL-18 and TNF-α) showed a linearly decrease (p < 0.01) with increasing dietary resveratrol level. These results demonstrated that resveratrol alleviated the LPS-induced acute ileitis of duck through Nrf2 and NF-κB signalling pathways, and the dietary resveratrol of 500 mg/kg is more efficiently.

Cross-Strand Interaction, Central Bending, and Sequence Pattern Act as Biomodulators of Simplified ß-Hairpin Antimicrobial Amphiphiles.

Novel antimicrobial peptides (AMPs) have revolutionarily evolved into formidable candidates for antibiotic substitute materials against pathogenic infections. However, cost, lability, disorderly sequences, systemic toxicology, and biological profiles have plagued the perennial search. Here, a progressive ß-hairpin solution with the simplest formulation is implanted into an AMP-based therapeutic strategy to systematically reveal the complex balance between function and toxicity of structural moieties, including cationicity, hydrophobicity, cross-strand interactions, center bending, and sequence pattern. Comprehensive implementation of structural identification, ten microorganisms, eleven in vitro barriers, four mammalian cells, and a diversified membrane operation setup led to the emergence of ß-hairpin prototypes from a 24-member library. Lead amphiphiles, WKF-PG and WRF-NG, can tackle bacterial infection through direct antimicrobial efficacy and potential inflammation-limiting capabilities, such as an Escherichia coli challenge in a mouse peritonitis-sepsis model, without observed toxicity after systemic administration. Their optimal states with dissimilar modulators and the unavailable drug resistance related to membrane lytic mechanisms, also provide an usher for renewed innovation among ß-sheet peptide-based antimicrobial biomaterials.

Design and heterologous expression of a novel dimeric LL37 variant in Pichia pastoris.

BACKGROUND: The antimicrobial peptide LL37 is produced by white blood cells (mainly neutrophils) and various epithelial cells, and has the outstanding advantages of participating in immune regulation, causing chemotaxis of immune cells and promoting wound healing. However, the central domain of LL37 needs to be improved in terms of antimicrobial activity. RESULTS: In this study, the amino acid substitution method was used to improve the antimicrobial activity of the LL37 active center, and a dimeric design with a better selection index was selected. A flexible linker was selected and combined with the 6 × His-SUMO tag and LG was successfully expressed using Pichia pastoris as a host. Recombinant LG displayed strong antimicrobial activity by destroying the cell membrane of bacteria but had low hemolytic activity. In addition, compared with monomeric peptide FR, rLG had improved ability to tolerate salt ions. CONCLUSION: This research provides new ideas for the production of modified AMPs in microbial systems and their application in industrial production.

De novo design of a pH-triggered self-assembled ß-hairpin nanopeptide with the dual biological functions for antibacterial and entrapment.

BACKGROUND: Acid-tolerant enteric pathogens can evade small intestinal acid barriers, colonize and infect the intestinal tract. However, broad-spectrum antibiotics are not the best therapeutic strategy because of the disruption of intestinal flora caused by its indiscriminate antimicrobial activity against beneficial and harmful bacteria. So that is what inspired us to combine pH regulation with nanotechnology to develop a pH-triggered site-targeted antimicrobial peptide with entrapping function. RESULTS: A pH-triggered dual biological functional self-assembled peptide (SAP) was designed according to the features of amino-acid building blocks and the diagonal cation-π interaction principle. The results of characterization experiments showed that changes in pH conditions could trigger microstructural transformation of the nanopeptide from nanospheres to nanofibers. The subsequent antibacterial and toxicity experiments determined that SAP had great antimicrobial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Bacillus cereus above 15.6 µg/mL under acidic conditions by disrupting bacterial membrane integrity, excellent biocompatibility in vitro even at 250 µg/mL and high tolerance in physical environment. Moreover, at peptide concentrations greater than 62.5 µg/mL, SAP showed the entrapment property, which played an important role in phagocytic clearance in infection forces. Meanwhile, the in vivo results revealed that SAP possessed excellent therapeutic effect and good biosafety. CONCLUSIONS: Our study revealed the antibacterial activity of a short ß-hairpin forming self-assembled peptide, and established an innovative design strategy for peptide-based nanomaterials and a new treatment strategy for gastrointestinal bacterial infections.

Selective Antifungal Activity and Fungal Biofilm Inhibition of Tryptophan Center Symmetrical Short Peptide.

Candida albicans, an opportunistic fungus, causes dental caries and contributes to mucosal bacterial dysbiosis leading to a second infection. Furthermore, C.albicans forms biofilms that are resistant to medicinal treatment. To make matters worse, antifungal resistance has spread (albeit slowly) in this species. Thus, it has been imperative to develop novel, antifungal drug compounds. Herein, a peptide was engineered with the sequence of RRFSFWFSFRR-NH2; this was named P19. This novel peptide has been observed to exert disruptive effects on fungal cell membrane physiology. Our results showed that P19 displayed high binding affinity to lipopolysaccharides (LPS), lipoteichoic acids (LTA) and the plasma membrane phosphatidylinositol (PI), phosphatidylserine (PS), cardiolipin, and phosphatidylglycerol (PG), further indicating that the molecular mechanism of P19 was not associated with the receptor recognition, but rather related to competitive interaction with the plasma membrane. In addition, compared with fluconazole and amphotericin B, P19 has been shown to have a lower potential for resistance selection than established antifungal agents.

Astragalus polysaccharides alleviates LPS-induced inflammation via the NF-κB/MAPK signaling pathway.

Early weaning usually causes intestinal disorders, enteritis, and diarrhea in young animals and human infants. Astragalus polysaccharides (APS) possesses anti-inflammatory activity. To study the anti-inflammatory mechanisms of APS and its potential effects on intestinal health, we performed an RNA sequencing (RNA-seq) study in lipopolysaccharide (LPS)-stimulated porcine intestinal epithelial cells (IPEC-J2) in vitro. In addition, LPS-stimulated BALB/c mice were used to study the effects of APS on intestinal inflammation in vivo. The results from the RNA-seq analysis show that there were 107, 756, and 5 differentially expressed genes in the control versus LPS, LPS versus LPS+APS, and control versus LPS+APS comparison groups, respectively. The results of Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways play significant roles in the regulation of inflammatory factors and chemokine expression by APS. Further verification of the above two pathways by using western blot and immunofluorescence analysis revealed that the gene expression levels of the phosphorylated p38 MAPK, ERK1/2, and NF-κB p65 were inhibited by APS, while the expression of IκB-α protein was significantly increased (p < .05), indicating that APS inhibits the production of inflammatory factors and chemokines by the inhibition of activation of the MAPK and NF-κB inflammatory pathways induced by LPS stimulation. Animal experiments further demonstrated that prefeeding APS in BALB/c mice can alleviate the expression of the jejunal inflammatory factors interleukin 6 (IL-6), IL-Iß, and tumor necrosis factor-α induced by LPS stimulation and improve jejunal villus morphology.

Expression of T9W in Pichia pastoris and the protective roles of T9W in ICR Mice.

BACKGROUND: The purpose of this paper is to express the novel α-helical peptide T9W more efficiently using the Pichia pastoris expression system and to examine the role of T9W in ICR mice. RESULTS: The novel antimicrobial peptide T9W was expressed in P. pastoris X-33 by using the vector pPICZαA. Approximately 13 mg/L T9W was secreted from the culture and purified. The expressed peptide has similar activity to the synthetic peptide. ICR female mice challenged with P. aeruginosa 27853 at the LD100 were treated with T9W and CPFX. The results showed that the secretion of inflammatory cytokines and lung damage was significantly reduced by the treatment group, and the protective response was equivalent between T9W and ciprofloxacin-treated mice. CONCLUSION: T9W was expressed in P. pastoris X-33 via the methanol-inducible vector pPICZαA and exhibited the same biological activity as synthetic T9W. T9W can alleviate damage to mice caused by P. aeruginosa.