Effects of probiotics supplementation on dementia and cognitive impairment: A systematic review and meta-analysis of preclinical and clinical studies

Background Dementia is a chronic syndrome characterized by cognitive and behavioral symptoms, which may include short-term memory impairment and problems related to orientation, language, attention and perception. Although cognitive impairment (CI) is increasingly considered the main geriatric condition predisposing to dementia, its early management could still promote symptomatic relief and delay disease progression. Recently, probiotics treatment has been studied as a potential new therapeutic approach to attenuate dementia-related decline and mild cognitive impairment (MCI). Therefore, we conducted a systematic review and meta-analysis to review and analyse the available evidence on the effect of probiotics on MCI and dementia. Methods A systematic search and meta-analysis were performed on Cochrane Library, ProQuest, Web of Science, PubMed-Medline, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, ScienceDirect and Open Grey. Search terms included diagnoses of interest (dementia and MCI) and the intervention of interest (probiotic, lactobacillus and bifidobacterium). Original articles reporting the use of probiotics supplementation for the treatment of dementia and MCI were screened and studied independently by two researchers. After that, a random and fixed effects model was used at the meta-analysis stage of the results to determine its effect size. Results A total of 16 articles (10 preclinical and 6 clinical) that met the inclusion criteria for the systematic review, and 15 articles (10 preclinical and 5 clinical) for meta-analysis were finally included. In humans, the administration of probiotics improved general cognitive function after the treatment period. Similarly, an improvement in memory and spatial/non-spatial learning was identified in the probiotic group of animals compared to the control group. On the other hand, the results showed an increase in the levels of the brain-derived neurotrophic factor, an improvement in the inflammatory profile and regulation of cellular biomarkers after probiotics administration. Conclusion Probiotics supplementation could be an adequate therapeutic strategy both in dementia and CI based on clinical and preclinical evidence. However, it is therefore important to translate preclinical data into clinical data where the evidence is more limited

Effects of probiotics on cognitive and emotional functions in healthy older adults: Protocol for a double-blind randomized placebo-controlled crossover trial

Aging is a process that includes changes in cognitive and emotional functions,as well as changes in the diversity and integrity of gut microbiota. Probiotictreatments have recently been studied as a potential new therapeutic approachto alleviate a wide range of problems in other populations; however, clinicalstudies in older adults remain insufficient and limited. Thus, the aim of thisproject is to evaluate the efficacy of a multispecies probiotic formulation as atherapeutic strategy for attenuating the emotional and cognitive decline asso-ciated with aging in adults over the age of 55. This is a double‐blind randomizedplacebo‐controlled crossover trial involving at least 32 older adults andcomparing two conditions: (a) probiotic, providing a multispecies probiotic for10 weeks (Lactobacillus rhamnosusandBifidobacterium lactis); and (b) placebo,receiving a harmless substance (potato starch). Despite the increasing use ofprobiotics for the treatment of cognitive and emotional problems, no study hasyet focused on this group, to the best of our knowledge. Therapeutic strategiesof the kind outlined in this protocol will help to shed light on the current state ofknowledge about this topic, as well as promote health programs tailored to thispopulation, which would encourage active aging and healthy lifestyles. Not onlydo we expect improvements in the emotional dimension in terms of anxiety,stress, depression, and sleep quality, we also expect improvements in the cog-nitive dimension in terms of attention,memory, and decreased impulsivity

Generation and integrated analysis of advanced patient-derived orthoxenograft models (PDOX) for the rational assessment of targeted therapies in endometrial cancer

Clinical management of endometrial cancer (EC) is handicapped by the limited availability of second line treatments and bona fide molecular biomarkers to predict recurrence. These limitations have hampered the treatment of these patients, whose survival rates have not improved over the last four decades. The advent of coordinated studies such as The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA_UCEC) has partially solved this issue, but the lack of proper experimental systems still represents a bottleneck that precludes translational studies from successful clinical testing in EC patients. Within this context, the first study reporting the generation of a collection of endometrioid-EC-patient-derived orthoxenograft (PDOX) mouse models is presented that is believed to overcome these experimental constraints and pave the way toward state-of-the-art precision medicine in EC. The collection of primary tumors and derived PDOXs is characterized through an integrative approach based on transcriptomics, mutational profiles, and morphological analysis; and it is demonstrated that EC tumors engrafted in the mouse uterus retain the main molecular and morphological features from analogous tumor donors. Finally, the molecular properties of these tumors are harnessed to assess the therapeutic potential of trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor with growing interest in EC, using patient-derived organotypic multicellular tumor spheroids and in vivo experiments

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

International audienceno abstrac

Effects of probiotics on cognitive and emotional functions in healthy older adults: Protocol for a double-blind randomized placebo-controlled crossover trial.

Aging is a process that includes changes in cognitive and emotional functions, as well as changes in the diversity and integrity of gut microbiota. Probiotic treatments have recently been studied as a potential new therapeutic approach to alleviate a wide range of problems in other populations; however, clinical studies in older adults remain insufficient and limited. Thus, the aim of this project is to evaluate the efficacy of a multispecies probiotic formulation as a therapeutic strategy for attenuating the emotional and cognitive decline associated with aging in adults over the age of 55. This is a double-blind randomized placebo-controlled crossover trial involving at least 32 older adults and comparing two conditions: (a) probiotic, providing a multispecies probiotic for 10 weeks (Lactobacillus rhamnosus and Bifidobacterium lactis); and (b) placebo, receiving a harmless substance (potato starch). Despite the increasing use of probiotics for the treatment of cognitive and emotional problems, no study has yet focused on this group, to the best of our knowledge. Therapeutic strategies of the kind outlined in this protocol will help to shed light on the current state of knowledge about this topic, as well as promote health programs tailored to this population, which would encourage active aging and healthy lifestyles. Not only do we expect improvements in the emotional dimension in terms of anxiety, stress, depression, and sleep quality, we also expect improvements in the cognitive dimension in terms of attention, memory, and decreased impulsivity

ZAKα/P38 kinase signaling pathway regulates hematopoiesis by activating the NLRP1 inflammasome

Abstract Chronic inflammatory diseases are associated with hematopoietic lineage bias, including neutrophilia and anemia. We have recently identified that the canonical inflammasome mediates the cleavage of the master erythroid transcription factor GATA1 in hematopoietic stem and progenitor cells (HSPCs). We report here that genetic inhibition of Nlrp1 resulted in reduced number of neutrophils and increased erythrocyte counts in zebrafish larvae. We also found that the NLRP1 inflammasome in human cells was inhibited by LRRFIP1 and FLII, independently of DPP9, and both inhibitors regulated hematopoiesis. Mechanistically, erythroid differentiation resulted in ribosomal stress‐induced activation of the ZAKα/P38 kinase axis which, in turn, phosphorylated and promoted the assembly of NLRP1 in both zebrafish and human. Finally, inhibition of Zaka with the FDA/EMA‐approved drug Nilotinib alleviated neutrophilia in a zebrafish model of neutrophilic inflammation and promoted erythroid differentiation and GATA1 accumulation in K562 cells. In conclusion, our results reveal that the NLRP1 inflammasome regulates hematopoiesis and pave the way to develop novel therapeutic strategies for the treatment of hematopoietic alterations associated with chronic inflammatory and rare diseases

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes