Human Neural Stem Cell Systems to Explore Pathogen-Related Neurodevelopmental and Neurodegenerative Disorders

Building and functioning of the human brain requires the precise orchestration and execution of myriad molecular and cellular processes, across a multitude of cell types and over an extended period of time. Dysregulation of these processes affects structure and function of the brain and can lead to neurodevelopmental, neurological, or psychiatric disorders. Multiple environmental stimuli affect neural stem cells (NSCs) at several levels, thus impairing the normal human neurodevelopmental program. In this review article, we will delineate the main mechanisms of infection adopted by several neurotropic pathogens, and the selective NSC vulnerability. In particular, TORCH agents, i.e., Toxoplasma gondii, others (including Zika virus and Coxsackie virus), Rubella virus, Cytomegalovirus, and Herpes simplex virus, will be considered for their devastating effects on NSC self-renewal with the consequent neural progenitor depletion, the cellular substrate of microcephaly. Moreover, new evidence suggests that some of these agents may also affect the NSC progeny, producing long-term effects in the neuronal lineage. This is evident in the paradigmatic example of the neurodegeneration occurring in Alzheimer's disease

Antioxidant and Antimicrobial Activity of Algal and Cyanobacterial Extracts: An In Vitro Study

Algae and cyanobacteria, other than their nutritional value, possess different beneficial properties, including antioxidant and antimicrobial ones. Therefore, they can be considered functional ingredients in animal feed and natural substitutes for antibiotics. The aim of this study was to evaluate the antioxidant and antimicrobial capacity against porcine O138 E. coli of Ascophyllum nodosum, Chlorella vulgaris, Lithotamnium calcareum, Schizochytrium spp. as algal species and Arthrospira platensis as cyanobacteria. The antioxidant capacity was determined by ABTS Radical Cation Decolorization Assay testing at three different concentrations (100%; 75%; 50%). The growth inhibition effect of the extracts at concentrations of 25%, 12.5%, 6%, 3% and 1.5% against porcine O138 E. coli was genetically characterized by PCR to detect the presence of major virulence factors; this was evaluated by following the microdilution bacterial growth method. The ABTS assay disclosed that Ascophyllum nodosum was the compound with the major antioxidant properties (57.75 ± 1.44 percentage of inhibition; p < 0.0001). All the extracts tested showed growth inhibition activity at a concentration of 25%. Among all extracts, A. nodosum was the most effective, showing a significant growth inhibition of E. coli; in particular, the log(10) cells/mL of E. coli used as a control resulted in a significantly higher concentration of 25% and 12.5% after 4 h (8.45 ± 0.036 and 7.22 ± 0.025 log(10) cells/mL, respectively; p < 0.005). This also suggests a dose-dependent relationship between the inhibitory activity and the concentration. Also, a synergistic effect was observed on antioxidant activity for the combination of Ascophyllum nodosum and Lithotamnium calcareum (p < 0.0001). Moreover, to determine if this combination could affect the viability of the IPEC-J2 cells under the normal or stress condition, the viability and membrane integrity were tested, disclosing that the combination mitigated the oxidative stress experimentally induced by increasing the cell viability. In conclusion, the results obtained highlight that the bioactive compounds of algal species are able to exert antioxidant capacity and modulate O138 E. coli growth. Also, the combination of Ascophyllum nodosum and Lithotamnium calcareum species can enhance their bioactivity, making them a promising functional feed additive and a suitable alternative to antibiotics

Lysozyme–Mineral Clay Systems: Comparison of Interaction for Controlled Release in Feed Application

A synthetic approach to bond lysozyme (LY) to commercial natural carriers, namely clay minerals (bentonite, BN; and sepiolite, SP) and commercial zeolite (Phil 75((R)), PH), already in use in feed formulation, is proposed. The synthetic route, which implies solid-liquid adsorption, is a simple and effective way for preparing hybrid materials characterized by LY loadings up to 37 mg(LY)/g(carrier). By operating at pH 4.3, initial LY content of 37.5 mg(LY)/g(carrier), and reaction time of 90 min, hybrid materials with LY loadings of 37, 35, and 12 mg(LY)/g(carrier) for LY-SP, LY-BN, and LY-PH, respectively were obtained. The LY initial concentration and pH, as well as the physico-chemical properties of the carries were found to be the parameters that govern the synthesis of the materials. The driving force for an effective LY adsorption and interaction is the combined Zero Point Charge (ZPC) of the carriers, always negative (in the range between 4 and 170 mV) and the positive ZPC of LY, as well as the carrier morphology, characterized by mesoporosity (pore dimensions in the range of 5-12 nm). However, it is the interaction of charges of opposite sign that mainly affects LY loadings and bond strength. Based on SEM-EDX analysis, LY molecules are quite homogeneously spread onto the carriers' surface. TG-DTG analyses showed that the LY-carrier interaction in the hybrid materials is stronger than that in a simple mechanical mixture of the components. Specifically, in the hybrid materials, the phenomenon at 300 degrees C, associated to LY decomposition, is broadened and slightly shifted towards higher temperatures (320-350 degrees C), whereas in a mechanical mixture of the same composition, it occurs at temperatures closer to those of free LY, as if there were no or very weak interactions. At pH 3, a very little LY release, 0.03 and 0.01 mg(LY)/g(carrier), was found for LY-BN and LY-PH, respectively. The latter became larger at pH 7, 0.06 mg(LY)/g(carrier) for both BN and PH carriers, suggesting that BN and PH are better modulators of LY release. The paper provides insights for the study and the development of new optimized feed formulations for the targeted delivery of natural compounds with antimicrobial activity, alternatives to antibiotics, and vaccinal antigens

The impact of knowledge management on the digital supply chain - a bibliometric literature review

PurposeUsing an abductive perspective, this study aims to review the scientific literature about the governance and management of the digital supply chain (DSC) in the context of the business organizations, providing an overview of the state of the art of the research and outlining a future research agenda with a knowledge management (KM) focus.Design/methodology/approachAfter investigating the Scopus database, 54 articles were identified as relevant and then subjected to an initial discernment. After this assessment, 34 articles focusing on operations management were further analyzed through both a bibliometric analysis and a content analysis.FindingsThe DSC represents a research area of increasing attention, with relevant contributions to several aspects of the field, as well as about KM. At the same time, the results show that the scientific literature on DSC models, solutions and applications is fragmented. Although the analysis has found a heterogeneous literature, two main streams of research seem to emerge: KM in the business culture development about DSC and KM in the business technological evolution about DSC.Originality/valueAlthough there exists growing interest in the scientific community, or perhaps because of this, area of research remains fragmented and under-theorized, thus requiring more systematic studies considering both economic and social aspects of the DSC. This study aims to provide innovative insights about this evolution, especially highlighting the two main contributions of KM in DSCs that have been revealed (business culture development and business technological evolution)

Evaluation of tributyrin supplementation in milk replacer on diarrhoea occurrence in preweaning Holstein calves

Neonatal calf diarrhoea is one of the most important health challenges in cattle herds causing substantial economic losses and antimicrobial use. Due to the raising problem of antimicrobial resistance, effective alternatives are urgently required, in line with European policies. The aim of this study was to evaluate the effect of tributyrin supplementation in milk replacer on diarrhoea, performance and metabolic status in preweaning Holstein calves. Twelve newborn calves, after colostrum administration, were randomly allotted in two experimental groups for 42 days: control (CTRL) fed milk replacer, tributyrin (TRIB) fed milk replacer supplemented with 0.3% of liquid tributyrin on milk powder weight. Calves BW was recorded on a weekly basis from day 7 to day 42, and feed intake was recorded daily to calculate zootechnical performance. Faecal consistency was assessed daily through the faecal score (0–3 scale; considering diarrhoea moderate = 2 and severe = 3). Faecal samples were collected weekly from rectal ampulla for microbiological analysis by plate counting method evaluating the number of total bacteria, lactic acid bacteria and coliform bacteria. On day 0 and day 42, individual blood samples were collected from jugular vein for metabolic profile analysis. Serum samples of day 42 were also evaluated for the antioxidant barrier using a colorimetric test, while glucagon-like peptide 2 and diamine oxidase concentrations were measured through immunoenzymatic assays. Tributyrin supplementation did not influence the zootechnical performance of calves over 42 days of trial. Diarrhoea frequency was significantly lower in TRIB compared to CTRL group (27.91 and 38.37%; P < 0.01) considering the whole experimental period. In particular, the major effect was observed for moderate diarrhoea in TRIB group that showed a significantly reduced frequency compared to CTRL (P < 0.01) thus suggesting a preventive effect of tributyrin. Faecal total bacterial, lactic acid and coliform bacteria counts did not show differences between groups. Urea serum concentrations tended to be lower in TRIB compared to CTRL, indicating an efficient utilisation of dietary protein. Antioxidant barrier and glucagon-like peptide 2 were comparable between CTRL and TRIB on day 42. Diamine oxidase concentrations were significantly decreased in TRIB compared to CTRL group after 42 days of trial (P < 0.01), suggesting a higher gut epithelial integrity probably due to lower diarrhoea frequency and the nourish effect of tributyrin on enterocytes. In conclusion, tributyrin could be considered as a valuable bioactive feed additive to decrease the neonatal diarrhoea occurrence and support intestinal integrity in preweaning calves

Protective effect of phytogenic plus short and medium-chain fatty acids-based additives in enterotoxigenic Escherichia coli challenged piglets

Post Weaning Diarrhea (PWD) is the most important multifactorial gastroenteric disease of the weaning in pig livestock. Phytogenic (PHY) natural extracts are largely studied as alternatives to antibiotic treatments in combating the global concern of the antimicrobial resistance. The aim of this study was to evaluate the protective effect of innovative phytogenic premix with or without short and medium chain fatty acids (SCFA and MCFA) in O138 Escherichia coli challenged piglets. Twenty-seven weaned piglets were allotted into four groups fed different diets according to the following dietary treatments: CTRL (n= 13) group fed basal diet, PHY1 (n= 7) fed the basal diet supplemented with 0.2% of phytogenic premix, PHY2 (n= 7) fed the basal diet supplemented with 0.2% of phytogenic premix added with 2000 ppm of SCFA and MCFA. After 6 days of experimental diet feeding, animals were challenged (day 0) with 2 x 10(9) CFU of E. coli and CTRL group was divided at day 0 into positive (challenged CTRL + ; n= 6) and negative control group (unchallenged CTRL-; n=7). Body weights were recorded at -14, -6, 0, 4 and 7 days and the feed intake was recorded daily. E. coli shedding was monitored for 4 days post-challenge by plate counting. Fecal consistency was registered daily by a four-point scale (0-3; diarrhea > 1) during the post-challenge period. Tissue samples were obtained for gene expression and histological evaluations at day 7 from four animals per group. Lower average feed intake was observed in CTRL + compared to PHY2 and CTRL during the post-challenge period. Infected groups showed higher E. coli shedding compared to CTRL- during the 4 days post-challenge (p < 0.01). PHY2 showed lower frequency of diarrhea compared to PHY1 and CTRL + from 5 to 7 days post-challenge. No significant alterations among groups were observed in histopathological evaluation. Duodenum expression of occludin tended to be lower in challenged groups compared to CTRL- at 7 days post-challenge (p= 0.066). In conclusion, dietary supplementation of PHY plus SCFA and MCFA revealed encouraging results for diarrhea prevention and growth performance in weaned piglets