A Target for Protective Interventions against Parkinson’s Disease

Funding Information: This research was funded by FWO and F.R.S.-FNRS under the Excellence of Science Program (EOS), MODEL-IDI Ref. number 30826052, and CD-INFLADIS Ref. number 40007512. A.C.P. is funded by FCT SFRH/BD/14611/2019. I.S.L was funded by FCT SFRH/BD/114552/2016 and is funded by MODEL-IDI Ref. number 30826052; A.C.M. was funded by FCT SFRH/BD/104599/2014; R.G. was funded by FCT IF 01495/2015. Publisher Copyright: © 2023 by the authors.Sub-chronic inflammation, caused by age-related dysbiosis, primes the brain to neuroinflammation and neurodegenerative diseases. Evidence revealed that Parkinson’s disease (PD) might originate in the gut, demonstrating gastro-intestinal disturbances, as reported by PD patients long before developing motor symptoms. In this study, we conducted comparative analyses in relatively young and old mice maintained in conventional or gnotobiotic conditions. We aimed to confirm that the effects induced by age-related dysbiosis, rather than aging itself, sensitize to PD onset. This hypothesis was confirmed in germ-free (GF) mice, which proved resistant to the pharmacological induction of PD, regardless of their age. Contrary to conventional animals, old GF mice did not develop an inflammatory phenotype or an accumulation of iron in the brain, two catalysts sensitizing to disease onset. The resistance of GF mice to PD is reverted when colonized with stool collected from conventional old animals, but not if receiving bacterial content from young mice. Hence, changes in gut microbiota composition are a risk factor for PD development and can be targeted preventively by iron chelators, shown to protect the brain from pro-inflammatory intestinal priming that sensitizes to neuroinflammation and the development of severe PD.publishersversionpublishe

Sensory profiling of complex meals : the case study of baked cod with cream and duck

Sensory analysis provides important information for developing new products and improving existing ones on the market. In fact, this science appears as a link between research and the development of innovative foods and their acceptance by the consumer [1]. The main purpose of this study is to evaluate the effectiveness of sensory methodologies for profiling of complex meals such as baked cod with cream and duck rice. Evaluation was performed with two sets of eight samples of industrial cod with cream and duck rice. Two independent trained panels of 9 and 12 judges evaluated the samples according to Quantitative Descriptive Analysis (QDA). Two independent panels of 16 untrained judges applied the Flash-Profile (FP) methodology over four sessions: attribute generation; final attribute list choice; evaluation 1 and 2. Two consumer panels evaluated the overall acceptance of each set of samples, on a sequential monadic presentation. For duck rice meals, the correlation between QDA and FP was not high (RV=0,646), and consumers preferred samples characterized by rice colour intensity, amount of duck, oiliness, bacon and chorizo in the meal. For cod with cream meals, the consumers preferred the samples characterized by amount and size of the cod pieces and intensity of cod taste, with a high correlation between FP and QDA (RV=0,860). Both sensory descriptive methodologies provide us with reliable and robust data in the characterization of complex meals. The FP methodology is relevant when working with panels of consumers to the extent that allows it to use their own lexicon of attributes. The application of external preference mapping on consumers’ response to FP emerges as a quick tool, either to describe products or to be used by food companies that have difficulties in using trained assessors’ panels. References: [1] Siegrist, M. (2008) Factors influencing public acceptance of innovative food technologies and products. Trends in Food Science & Technology, 19, 603-608

Role of protein kinase R in the killing of Leishmania major by macrophages in response to neutrophil elastase and TLR4 via TNF and IFN

In cutaneous leishmaniasis, Leishmania amazonensis activates macrophage double-stranded, RNA-activated protein kinase R (PKR) to promote parasite growth. In our study, Leishmania major grew normally in RAW cells, RAW-expressing dominant-negative PKR (PKR-DN) cells, and macrophages of PKR-knockout mice, revealing that PKR is dispensable for L. major growth in macrophages. PKR activation in infected macrophages with poly I:C resulted in parasite death. Fifty percent of L. major-knockout lines for the ecotin-like serine peptidase inhibitor (ISP2; Δisp2/isp3), an inhibitor of neutrophil elastase (NE), died in RAW cells or macrophages from 129Sv mice, as a result of PKR activation. Inhibition of PKR or NE or neutralization of Toll-like receptor 4 or 2(TLR4 or TLR2) prevented the death of Δisp2/isp3. Δisp2/isp3 grew normally in RAW-PKR-DN cells or macrophages from 129Sv pkr−/−, tlr2−/−, trif−/−, and myd88−/− mice, associating NE activity, PKR, and TLR responses with parasite death. Δisp2/isp3 increased the expression of mRNA for TNF-α by 2-fold and of interferon β (IFNβ) in a PKR-dependent manner. Antibodies to TNF-α reversed the 95% killing by Δisp2/isp3, whereas they grew normally in macrophages from IFN receptor–knockout mice. We propose that ISP2 prevents the activation of PKR via an NE-TLR4-TLR2 axis to control innate responses that contribute to the killing of L. major.—Faria, M. S., Calegari-Silva, T. C., de Carvalho Vivarini, A., Mottram, J. C., Lopes, U. G., Lima, A. P. C. A. Role of protein kinase R in the killing of Leishmania major by macrophages in response to neutrophil elastase and TLR4 via TNFα and IFNβ

MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease

AbstractIntroductionMononuclear phagocytes play a critical role during Alzheimer's disease (AD) pathogenesis due to their contribution to innate immune responses and amyloid beta (Aβ) clearance mechanisms.MethodsBlood-derived monocytes (BDMs) and monocyte-derived macrophages (MDMs) were isolated from blood of AD, mild cognitive impairment (MCI) patients, and age-matched healthy controls for molecular and phenotypic comparisons.ResultsThe chemokine/chemokine receptor CCL2/CCR2 axis was impaired in BDMs from AD and MCI patients, causing a deficit in cell migration. Changes were also observed in MDM-mediated phagocytosis of Aβ fibrils, correlating with alterations in the expression and processing of the triggering receptor expressed on myeloid cells 2 (TREM2). Finally, immune-related microRNAs (miRNAs), including miR-155, -154, -200b, -27b, and -128, were found to be differentially expressed in these cells.DiscussionThis work provides evidence that chemotaxis and phagocytosis, two crucial innate immune functions, are impaired in AD and MCI patients. Correlations with miRNA levels suggest an epigenetic contribution to systemic immune dysfunction in AD

Prebiotics : from concept to product : the BIOLIFE project

Nutrition has progressed from the discovery of essential nutrients and prevention of dietary deficiency to the promotion of a state of well-being and health and the reduction of the risk of disease. In this context the functional food concept emerges: a food or drink product that, when ingested, exerts particular benefits on some physiological functions. The gastrointestinal functions are associated with a balanced colonic microflora that plays a key role in individual health. This complex ecosystem can be modulated by the ingestion of dietary components that favour the growth and metabolism of beneficial indigenous species such as bifidobacteria and lactobacilli. These components of saccharidic nature are called prebiotics. The BIOLIFE project involves the development of novel biotechnological processes, enzymatic and fermentative, for the production of prebiotics, namely, galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS) from food industry by-products. Produced oligosaccharides will be incorporated in liquid and solid food formulations in order to obtain functional foods targeted towards gut function.Fundação para a Ciência e a Tecnologia (FCT)

Assisted Reproductive Techniques on South American Wild Mammals

For South American wild mammals, assisted reproductive techniques (ARTs) have been established in accordance with the procedures used for domestic mammals. However, often, it is not possible to infer the experimental conditions from one species to another. In general, the use of these ARTs aims the conservation of the animal genetic material, using gamete manipulation, embryo technology by in vivo or in vitro methods, and cloning. In all animals, the previous knowledge of reproductive physiology becomes the starting point for the use of ARTs in the expansion of all species of interest. In this sense, the purpose of this chapter is to develop an approach of theoretical, technical, and applied aspects of the ARTs in South American wild mammals, with emphasis on the state-of-the-art and its progress and perspectives

Tailor made degradable ureteral stents from natural origin polysaccharides

A urinary stent is defined as a thin tube, which is inserted in the ureter to prevent or treat the obstruction of urine flow from the kidney. Silicone, latex, polyvinylchloride and polyurethanes are the most widely used materials for the preparation of stents. Nonetheless, severe clinical complications may result from the use of these materials such as fracture, encrustation and infection. In some of the cases, the ureteral stents are temporary and it is often required a second surgery to remove the stent. The main complications with ureteral stents are dislocation, infection, and blockage by encrustation [1]. Recently, a tendency has been noticed favouring less invasive approaches (e.g. pharmacological or catheterization) in treating patients who exhibit symptoms or signs of urinary retention [2]. Currently, nearly 100% of the people who have an urological stent are likely to develop a bacterial infection within 30 days, which increases morbidity threefold [1]. Different types of temporary and permanent stents have been introduced into urological practice to relieve obstructions [3]. Particular attention should be devoted to polymers as they represent a highly versatile class of materials. Despite the fact that silicon continues to be the gold standard material for urological stents, there have been fast developments in manufacturing processes, as well as the introduction of new biodegradable materials in order to overcome the drawbacks of the available products. Polyurethane continues to be the most widely used material for polymeric stents; however it frequently promotes biofilm formation and bacterial adhesion leading to severe infections [2]. The concerns regarding existing stents are the motivation to design new biodegradable urological stent systems based on natural polymers, specifically polysaccharides, which present inherent biocompatibility, anti-bacterial properties and that can be tailor-made into a custom suitable stent for a particular patient

Variations in salivary function in a rodent model of pre-diabetes

Diabetes is a widespread disease representing an enormous part of the total health costs. An early diagnostic could be of extremely importance both for the understanding and prevention of this pathology. Saliva is a fluid with increasing interest as a source of biomarkers for disease diagnostic and saliva protein composition changes have already been reported for diabetic individuals. However, the studies were performed after the onset of the disease and it is unknown if salivary changes are present in the early stages of development of the disease or a characteristic of overt diabetes. Wistar rats have been selected for their glucose intolerance (GIR). GIR females were compared with Wistar females with normal glucose tolerance (control) for changes in saliva protein composition and salivary gland histology. Fasting glycemias were observed to be normal (<95 mg/dl) in GIR animals, indicating an absence of a diabetic state. However they presented an abnormal increase in glycemia after a glucose bolus. For salivary parameters a marked increase in total protein concentration and alpha-amylase activity occurred in GIR animals, comparatively to controls. After separation of salivary proteins by SDS PAGE differences between the experimental groups for some protein bands, with apparent molecular masses ranging from 20 to 55 kDa were observed. Different expression of alphaamylase at salivary gland duct level is also apparent for pre-diabetic animals. Although preliminary, these results suggest changes in saliva occurring before the onset of diabetes, reinforcing the interest of further investigation of saliva composition for the diagnostic of pre-diabetic condition, ultimately allowing an early intervention and eventually the prevention of disease development