Nutritional, molecular, and functional properties of a novel enzymatically hydrolyzed porcine plasma product.

In the present study, an enzymatically hydrolyzed porcine plasma (EHPP) was nutritionally and molecularly characterized. EHPP molecular characterization showed, in contrast to spray-dried plasma (SDP), many peptides with relative molecular masses (Mr) below 8,000, constituting 73% of the protein relative abundance. IIAPPER, a well-known bioactive peptide with anti-inflammatory and antioxidant properties, was identified. In vivo functionality of EHPP was tested in C. elegans and two different mouse models of intestinal inflammation. In C. elegans subjected to lipopolysaccharide exposure, EHPP displayed a substantial anti-inflammatory effect, enhancing survival and motility by 40% and 21.5%, respectively. Similarly, in mice challenged with Staphylococcus aureus enterotoxin B or Escherichia coli O42, EHPP and SDP supplementation (8%) increased body weight and average daily gain while reducing the percentage of regulatory Th lymphocytes. Furthermore, both products mitigated the increase of pro-inflammatory cytokines expression associated with these challenged mouse models. In contrast, some significant differences were observed in markers such as Il-6 and Tnf-α, suggesting that the products may present different action mechanisms. In conclusion, EHPP demonstrated similar beneficial health effects to SDP, potentially attributable to the immunomodulatory and antioxidant activity of its characteristic low Mr bioactive peptides.

WFA-GPU: gap-affine pairwise read-alignment using GPUs.

MOTIVATION: Advances in genomics and sequencing technologies demand faster and more scalable analysis methods that can process longer sequences with higher accuracy. However, classical pairwise alignment methods, based on dynamic programming (DP), impose impractical computational requirements to align long and noisy sequences like those produced by PacBio and Nanopore technologies. The recently proposed wavefront alignment (WFA) algorithm paves the way for more efficient alignment tools, improving time and memory complexity over previous methods. However, high-performance computing (HPC) platforms require efficient parallel algorithms and tools to exploit the computing resources available on modern accelerator-based architectures. RESULTS: This paper presents WFA-GPU, a GPU (graphics processing unit)-accelerated tool to compute exact gap-affine alignments based on the WFA algorithm. We present the algorithmic adaptations and performance optimizations that allow exploiting the massively parallel capabilities of modern GPU devices to accelerate the alignment computations. In particular, we propose a CPU-GPU co-design capable of performing inter-sequence and intra-sequence parallel sequence alignment, combining a succinct WFA-data representation with an efficient GPU implementation. As a result, we demonstrate that our implementation outperforms the original multi-threaded WFA implementation by up to 4.3× and up to 18.2× when using heuristic methods on long and noisy sequences. Compared to other state-of-the-art tools and libraries, the WFA-GPU is up to 29× faster than other GPU implementations and up to four orders of magnitude faster than other CPU implementations. Furthermore, WFA-GPU is the only GPU solution capable of correctly aligning long reads using a commodity GPU. AVAILABILITY AND IMPLEMENTATION: WFA-GPU code and documentation are publicly available at https://github.com/quim0/WFA-GPU.

Dietary supplementation with spray-dried animal plasma improves vaccine protection in aged mice.

Background: Senescence is characterized by an aggravated inflammatory state that reduces vaccine responsiveness. Dietary supplementation with spray-dried porcine plasma (SDP) exerts anti-inflammatory effects in different mucosal areas. We aimed to determine if the anti-inflammatory properties of SDP improve the efficiency of immunization in senescent animals. Methods: Experiments were performed in 2-month-old and 6-month-old male SAMP8 mice fed control or SDP (8%) feeds for 4 months. The mice received nasal doses of 2.5 µg of Staphylococcus aureus enterotoxin B (SEB) or vehicle every 15 days (i.e., 3 times). Fifteen days after the last dose, a lethal shock was induced by intraperitoneal administration of SEB and LPS. Results: Immunization increased anti-SEB IgA in intestinal and bronchoalveolar fluid (p < 0.05). After the lethal shock, all immunized aged mice that were supplemented with SDP survived, in contrast to only 66% of those fed the control feed (p < 0.05). Moreover, after the lethal challenge, aged mice showed higher expression levels of pro-inflammatory cytokines (Il-6, Tnf-α, Ifn-γ, and Il-1ß) in jejunal and (Tnf-α, and Il-1ß) in lung tissues (p < 0.05), which were reduced by SDP supplementation (p < 0.05). Furthermore, in senescent mice, SDP supplementation augmented Il-4 and Il-10 expression in both tissues (p < 0.05). Conclusion: SDP reduces the mucosal inflammation associated with aging, improving vaccine protection in senescent mice.

Porting and Optimizing BWA-MEM2 Using the Fujitsu A64FX Processor.

Sequence alignment pipelines for human genomes are an emerging workload that will dominate in the precision medicine field. BWA-MEM2 is a tool widely used in the scientific community to perform read mapping studies. In this paper, we port BWA-MEM2 to the AArch64 architecture using the ARMv8-A specification, and we compare the resulting version against an Intel Skylake system both in performance and in energy-to-solution. The porting effort entails numerous code modifications, since BWA-MEM2 implements certain kernels using x86_64 specific intrinsics, e.g., AVX-512. To adapt this code we use the recently introduced Arm's Scalable Vector Extensions (SVE). More specifically, we use Fujitsu's A64FX processor, the first to implement SVE. The A64FX powers the Fugaku Supercomputer that led the Top500 ranking from June 2020 to November 2021. After porting BWA-MEM2 we define and implement a number of optimizations to improve performance in the A64FX target architecture. We show that while the A64FX performance is lower than that of the Skylake system, A64FX delivers 11.6% better energy-to-solution on average. All the code used for this article is available at https://gitlab.bsc.es/rlangari/bwa-a64fx.

Dietary intake of table olives exerts antihypertensive effects in association with changes in gut microbiota in spontaneously hypertensive rats.

Arbequina table olive (AO) consumption lowers blood pressure (BP) in spontaneously hypertensive rats (SHR). This study evaluates whether dietary supplementation with AO induced changes in the gut microbiota that are consistent with the purported antihypertensive effects. Wistar-Kyoto rats (WKY-c) and SHR-c received water, while SHR-o were supplemented by gavage with AO (3.85 g kg-1) for 7 weeks. Faecal microbiota was analysed by 16S rRNA gene sequencing. SHR-c showed increased Firmicutes and decreased Bacteroidetes compared to WKY-c. AO supplementation in SHR-o decreased BP by approximately 19 mmHg, and reduced plasmatic concentrations of malondialdehyde and angiotensin II. Moreover, reshaped faecal microbiota associated with antihypertensive activity by lowering Peptoniphilus and increasing Akkermansia, Sutterella, Allobaculum, Ruminococcus, and Oscillospira. Also promoted the growth of probiotic strains of Lactobacillus and Bifidobacterium and modified the relationship of Lactobacillus with other microorganisms, from competitive to symbiotic. In SHR, AO promotes a microbiota profile compatible with the antihypertensive effects of this food.

Optimal gap-affine alignment in O(s) space.

MOTIVATION: Pairwise sequence alignment remains a fundamental problem in computational biology and bioinformatics. Recent advances in genomics and sequencing technologies demand faster and scalable algorithms that can cope with the ever-increasing sequence lengths. Classical pairwise alignment algorithms based on dynamic programming are strongly limited by quadratic requirements in time and memory. The recently proposed wavefront alignment algorithm (WFA) introduced an efficient algorithm to perform exact gap-affine alignment in O(ns) time, where s is the optimal score and n is the sequence length. Notwithstanding these bounds, WFA's O(s2) memory requirements become computationally impractical for genome-scale alignments, leading to a need for further improvement. RESULTS: In this article, we present the bidirectional WFA algorithm, the first gap-affine algorithm capable of computing optimal alignments in O(s) memory while retaining WFA's time complexity of O(ns). As a result, this work improves the lowest known memory bound O(n) to compute gap-affine alignments. In practice, our implementation never requires more than a few hundred MBs aligning noisy Oxford Nanopore Technologies reads up to 1 Mbp long while maintaining competitive execution times. AVAILABILITY AND IMPLEMENTATION: All code is publicly available at https://github.com/smarco/BiWFA-paper. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Neuroprotective Effects of Spray-Dried Porcine Plasma Supplementation Involve the Microbiota-Gut-Brain Axis.

Dietary supplementation with spray-dried porcine plasma (SDP) reduces the Alzheimer's disease (AD) hallmarks in SAMP8 mice. Since gut microbiota can play a critical role in the AD progression, we have studied if the neuroprotective effects of SDP involve the microbiota−gut−brain axis. Experiments were performed on two-month-old SAMP8 mice fed a standard diet and on six-month-old SAMP8 mice fed a control diet or an 8% SDP supplemented diet for four months. Senescence impaired short- and long-term memory, reduced cortical brain-derived neurotrophic factor (BDNF) abundance, increased interleukin (Il)-1ß, Il-6, and Toll-like receptor 2 (Tlr2) expression, and reduced transforming growth factor ß (Tgf-ß) expression and IL-10 concentration (all p < 0.05) and these effects were mitigated by SDP (all p < 0.05). Aging also increased pro-inflammatory cytokines in serum and colon (all p < 0.05). SDP attenuated both colonic and systemic inflammation in aged mice (all p < 0.05). SDP induced the proliferation of health-promoting bacteria, such as Lactobacillus and Pediococcus, while reducing the abundance of inflammation-associated bacteria, such as Johnsonella and Erysipelothrix (both q < 0.1). In conclusion, SDP has mucosal and systemic anti-inflammatory effects as well as neuroprotective properties in senescent mice; these effects are well correlated with SDP promotion of the abundance of probiotic species, which indicates that the gut−brain axis could be involved in the peripheral effects of SDP supplementation.

Compressed Sparse FM-Index: Fast Sequence Alignment Using Large K-Steps.

The FM-index is a data structure used in genomics for exact search of input sequences over large reference genomes. Algorithms based on the FM-index show an irregular memory access pattern, resulting in a memory bound problem. We analyze a recent implementation of the FM-index and highlight existing throughput-memory trade-offs, showing that memory requirements limit implementation of large k-steps. We propose COFI, a COmpressed FM-Index for large K-steps. COFI enables a 15-step FM-index using less than 16 GB for a human genome reference of 3 giga base pairs. An algorithm based on this new layout is evaluated on both a Knights Landing (KNL) and an Skylake-based system (SKX). We achieve average speed-ups of 1.46× and 1.39×, respectively, with respect to an state-of-the-art FM-index implementation that is already well optimized.

AnchorWave: Sensitive alignment of genomes with high sequence diversity, extensive structural polymorphism, and whole-genome duplication.

Millions of species are currently being sequenced, and their genomes are being compared. Many of them have more complex genomes than model systems and raise novel challenges for genome alignment. Widely used local alignment strategies often produce limited or incongruous results when applied to genomes with dispersed repeats, long indels, and highly diverse sequences. Moreover, alignment using many-to-many or reciprocal best hit approaches conflicts with well-studied patterns between species with different rounds of whole-genome duplication. Here, we introduce Anchored Wavefront alignment (AnchorWave), which performs whole-genome duplication-informed collinear anchor identification between genomes and performs base pair-resolved global alignment for collinear blocks using a two-piece affine gap cost strategy. This strategy enables AnchorWave to precisely identify multikilobase indels generated by transposable element (TE) presence/absence variants (PAVs). When aligning two maize genomes, AnchorWave successfully recalled 87% of previously reported TE PAVs. By contrast, other genome alignment tools showed low power for TE PAV recall. AnchorWave precisely aligns up to three times more of the genome as position matches or indels than the closest competitive approach when comparing diverse genomes. Moreover, AnchorWave recalls transcription factor-binding sites at a rate of 1.05- to 74.85-fold higher than other tools with significantly lower false-positive alignments. AnchorWave complements available genome alignment tools by showing obvious improvement when applied to genomes with dispersed repeats, active TEs, high sequence diversity, and whole-genome duplication variation.

Reply to Nifli, A.-P. Comment on "Rosell-Cardona et al. Dietary Spray-Dried Porcine Plasma Reduces Neuropathological Alzheimer's Disease Hallmarks in SAMP8 Mice. Nutrients 2021, 13, 2369".

Thank you for your comments on our recent work of the effects of supplementation with spray-dried porcine plasma (SDP) on neuropathological markers of Alzheimer's disease (AD) [...].

Dietary Spray-Dried Porcine Plasma Reduces Neuropathological Alzheimer's Disease Hallmarks in SAMP8 Mice.

Alzheimer's disease (AD) is characterized by the aberrant processing of amyloid precursor protein (APP) and the accumulation of hyperphosphorylated tau, both of which are accompanied by neuroinflammation. Dietary supplementation with spray-dried porcine plasma (SDP) has anti-inflammatory effects in inflammation models. We investigated whether dietary supplementation with SDP prevents the neuropathological features of AD. The experiments were performed in 2- and 6-month-old SAMP8 mice fed a control diet, or a diet supplemented with 8% SDP, for 4 months. AD brain molecular markers were determined by Western blot and real-time PCR. Senescent mice showed reduced levels of p-GSK3ß (Ser9) and an increase in p-CDK5, p-tau (Ser396), sAPPß, and the concentration of Aß40, (all p < 0.05). SDP prevented these effects of aging and reduced Bace1 levels (all p < 0.05). Senescence increased the expression of Mme1 and Ide1 and pro-inflammatory cytokines (Il-17 and Il-18; all p < 0.05); these changes were prevented by SDP supplementation. Moreover, SDP increased Tgf-ß expression (p < 0.05). Furthermore, in aged mice, the gene expression levels of the microglial activation markers Trem2, Ym1, and Arg1 were increased, and SDP prevented these increases (all p < 0.05). Thus, dietary SDP might delay AD onset by reducing its hallmarks in senescent mice.

Fast gap-affine pairwise alignment using the wavefront algorithm.

MOTIVATION: Pairwise alignment of sequences is a fundamental method in modern molecular biology, implemented within multiple bioinformatics tools and libraries. Current advances in sequencing technologies press for the development of faster pairwise alignment algorithms that can scale with increasing read lengths and production yields. RESULTS: In this article, we present the wavefront alignment algorithm (WFA), an exact gap-affine algorithm that takes advantage of homologous regions between the sequences to accelerate the alignment process. As opposed to traditional dynamic programming algorithms that run in quadratic time, the WFA runs in time O(ns), proportional to the read length n and the alignment score s, using O(s2) memory. Furthermore, our algorithm exhibits simple data dependencies that can be easily vectorized, even by the automatic features of modern compilers, for different architectures, without the need to adapt the code. We evaluate the performance of our algorithm, together with other state-of-the-art implementations. As a result, we demonstrate that the WFA runs 20-300× faster than other methods aligning short Illumina-like sequences, and 10-100× faster using long noisy reads like those produced by Oxford Nanopore Technologies. AVAILABILITY AND IMPLEMENTATION: The WFA algorithm is implemented within the wavefront-aligner library, and it is publicly available at https://github.com/smarco/WFA.

Dietary Supplementation with Spray-Dried Porcine Plasma Attenuates Colon Inflammation in a Genetic Mouse Model of Inflammatory Bowel Disease.

Dietary supplementation with spray-dried porcine plasma (SDP) can modulate the immune response of gut-associated lymphoid tissue. SDP supplementation reduces acute mucosal inflammation, as well as chronic inflammation associated with aging. The aim of this study was to analyze if SDP supplementation could ameliorate colitis in a genetic mouse model of inflammatory bowel disease (IBD). Wild-type mice and Mdr1a knockout (KO) mice were administered a control diet or an SDP-supplemented diet from day 21 (weaning) until day 56. The histopathological index, epithelial barrier, and intestinal immune system were analyzed in the colonic mucosa. KO mice had higher epithelial permeability, increased Muc1 and Muc4 expression, and lower abundance of E-cadherin and Muc2 (all p < 0.001). SDP prevented these effects (all p < 0.05) and decreased the colonic inflammation observed in KO mice, reducing neutrophil and monocyte infiltration and activation and the percentage of activated T helper lymphocytes in the colonic mucosa (all p < 0.05). SDP also diminished proinflammatory cytokine expression and increased the anti-inflammatory IL-10 concentration in the colonic mucosa (all p < 0.05). In conclusion, dietary supplementation with SDP enhances colon barrier function and reduces mucosal inflammation in a mouse model of IBD.

Dietary Spray-Dried Porcine Plasma Prevents Cognitive Decline in Senescent Mice and Reduces Neuroinflammation and Oxidative Stress.

BACKGROUND: Aging is characterized by chronic, low-grade inflammation that correlates with cognitive decline. Dietary supplementation with spray-dried porcine plasma (SDP) reduces immune activation in rodent models of inflammation and aging. OBJECTIVE: We investigated whether the anti-inflammatory properties of SDP could ameliorate age-related cognitive deterioration and preserve brain homeostasis in an aging mouse model of senescence. METHODS: Male senescence-accelerated prone 8 (SAMP8) mice were used. In Experiment 1, cognitive performance (n  = 10-14 mice/group) was analyzed by the novel object recognition test in 2-mo-old mice (2M group) and in mice fed a control diet or a diet supplemented with 8% SDP for 2 (4M-CTL and 4M-SDP groups) and 4 mo (6M-CTL and 6M-SDP groups). In Experiment 2, the permeability of the blood-brain barrier and junctional proteins in brain tissue was assessed, as well as synaptic density, oxidative stress markers, and inflammatory genes and proteins in mice from the 2M, 6M-CTL, and 6M-SDP groups ( n = 5-11). Statistical analyses included one-factor ANOVA followed by Fisher's posthoc test. RESULTS: 6M-SDP mice had better cognitive performance than 6M-CTL mice in both short-term (P = 0.024) and long-term (P = 0.017) memory tests. In brain tissue, 6M-SDP mice showed reduced brain capillary permeability (P = 0.034) and increased ZO1 and E-cadherin expression (both P <0.04) compared with 6M-CTL mice. SDP also prevented the NFκB activation observed in 6M-CTL mice (P = 0.002) and reduced Il6 expression and hydrogen peroxide concentration (both P <0.03) observed in 6M-CTL mice. SDP also increased the concentration of IL10 (P = 0.027), an anti-inflammatory cytokine correlated with memory preservation. CONCLUSIONS: In senescent SAMP8 mice, dietary supplementation with SDP attenuated cognitive decline and prevented changes in brain markers of neuroinflammation and oxidative stress.

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice.

Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging) which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP), which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT) in rodents challenged by S. aureus enterotoxin B (SEB), and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8) at different ages (compared to mice resistant to accelerated senescence; SAMR1). Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer's patches (all, p < 0.05), as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05). With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05). However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

The Anti-Inflammatory Effect of Spray-Dried Plasma Is Mediated by a Reduction in Mucosal Lymphocyte Activation and Infiltration in a Mouse Model of Intestinal Inflammation.

Spray-dried preparations from porcine and bovine plasma can alleviate mucosal inflammation in experimental models and improve symptoms in patients with enteropathy. In rodents, dietary supplementation with porcine spray-dried plasma (SDP) attenuates intestinal inflammation and improves the epithelial barrier function during intestinal inflammation induced by Staphylococcus aureus enterotoxin B (SEB). The aim of this study was to discern the molecular mechanisms involved in the anti-inflammatory effects of SDP. Male C57BL/6 mice were fed with 8% SDP or control diet (based on milk proteins) for two weeks, from weaning until day 33. On day 32, the mice were given a SEB dose (i.p., 25 µg/mouse) or vehicle. SEB administration increased cell recruitment to mesenteric lymph nodes and the percentage of activated Th lymphocytes and SDP prevented these effects). SDP supplementation increased the expression of interleukin 10 (IL-10) or transforming growth factor- ß (TGF-ß) compared to the SEB group. The SEB challenge increased six-fold the expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) and intercellular adhesion molecule 1 (ICAM-1); and these effects were attenuated by SDP supplementation. SEB also augmented NF-κB phosphorylation, an effect that was prevented by dietary SDP. Our results indicate that the anti-inflammatory effects of SDP involve the regulation of transcription factors and adhesion molecules that reduce intestinal cell infiltration and the degree of the inflammatory response.

Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis.

Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT). Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI) ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% w/w) or milk proteins (Control diet), from day 21 (weaning) until day 56. Leucocytes in mesenteric lymph nodes (MLN) and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05). The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05) and SBI supplementation reduced this variable (p < 0.05). The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05). In the colon of KO mice, there was an increased production of mucosal pro-inflammatory cytokines such as IL-2 (2-fold), IL-6 (26-fold) and IL-17 (19-fold), and of chemokines MIP-1ß (4.5-fold) and MCP-1 (7.2-fold). These effects were significantly prevented by SBI (p < 0.05). SBI also significantly increased TGF-ß secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis.

Dietary intervention with serum-derived bovine immunoglobulins protects barrier function in a mouse model of colitis.

Dietary supplementation with immunoglobulins from animal plasma has anti-inflammatory effects on intestinal and lung models of acute inflammation. Here, we aimed to establish whether dietary intervention with serum-derived bovine immunoglobulin (SBI) can prevent alterations in intestinal barrier function in a mouse model with a genetic predisposition to inflammatory bowel disease (IBD). Wild-type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% wt/wt) or milk proteins (control diet), from day 21 (weaning) until day 56. The epithelial permeability of distal colon crypts was measured by confocal microscopy using a fluorescent marker. The expression of junctional epithelial E-cadherin and ß-catenin proteins were determined by Western blot and zonula occludens-1 (ZO-1) by immunofluorescence. Mucins (MUC1, MUC2, MUC4), TFF3, cytokines (TNF-α, IFN-γ), and inducible nitric oxide synthase RNA expression were quantified by real-time PCR. SBI blocked the increase in colon crypt permeability and partially prevented the reduction in E-cadherin and ZO-1 expression that characterize the KO mouse model (both P < 0.05). SBI inclusion also reduced the mucosal expression of the inflammatory markers TNF-α, IFN-γ, and inducible nitric oxide synthase (all P < 0.005). The number of goblet cells in the colon of KO mice was low and correlated well with MUC2 and TFF3 expression (P < 0.001), whereas dietary supplementation with SBI attenuated these effects (all P < 0.05). In short, dietary SBI ameliorated colonic barrier alterations and reduced the expression of mucosal inflammatory markers in a genetic model of IBD.

Type I interferon response is delayed in human astrovirus infections.

Type I interferon (IFN) activation and its subsequent effects are important in the response to viral infections. Here we show that human astroviruses (HAstVs), which are important agents of acute gastroenteritis in children, induce a mild and delayed IFN response upon infecting CaCo-2 cells. Although IFN-ß mRNA is detected within infected cells and supernatant from infected cells show antiviral activity against the replication of other well-known IFN-sensitive viruses, these responses occur at late stages of infection once genome replication has taken place. On the other hand, HAstV replication can be partially reduced by the addition of exogenous IFN, and inhibition of IFN activation by BX795 enhances viral replication, indicating that HAstVs are IFN-sensitive viruses. Finally, different levels of IFN response were observed in cells infected with different HAstV mutants with changes in the hypervariable region of nsP1a/4, suggesting that nsP1a/4 genotype may potentially have clinical implications due to its correlation with the viral replication phenotype and the antiviral responses induced within infected cells.

Vasopressin regulation of epithelial colonic proliferation and permeability is mediated by pericryptal platelet-derived growth factor A.

Arginine vasopressin (AVP) has trophic effects on the rat distal colon, increasing the growth of pericryptal myofibroblasts and reducing the colonic crypt wall permeability. This study aimed to reproduce in vitro the effects of AVP observed in vivo using cultures of human CCD-18Co myofibroblasts and T84 colonic epithelial cells. Proliferation of myofibroblasts was quantified by bromodeoxyuridine incorporation; the expression of platelet-derived growth factor A (PDGFA), platelet-derived growth factor B, epidermal growth factor, transforming growth factor-ß and vascular endothelial growth factor was measured by PCR and the expression of epithelial junction proteins by Western blot. Arginine vasopressin stimulated myofibroblast proliferation and the expression of PDGFA without affecting the expression of platelet-derived growth factor B, epidermal growth factor, transforming growth factor-ß or vascular endothelial growth factor. These effects were prevented when AVP receptor inhibitors were present in the medium. Pre-incubation of CCD-18Co cells with anti-PDGF antibody or with an inhibitor of the PDGF receptor abolished the effects of AVP. When colonocytes were incubated with medium obtained from myofibroblasts incubated with AVP, both cell proliferation and the expression of epithelial junction proteins increased; however, direct incubation of colonocytes with AVP did not modify these variables. These results demonstrate that AVP stimulates myofibroblast proliferation and induces PDGFA secretion, implying that PDGFA mediates local myofibroblast proliferation by an autocrine feedback loop and regulates epithelial proliferation and permeability by a paracrine mechanism.