A meta-analysis and systematic review of randomized controlled trials with degarelix versus gonadotropin-releasing hormone agonists for advanced prostate cancer

Our aim was to systematically evaluate the benefits of degarelix as antagonist versus agonists of gonadotropin-releasing hormones (GnRH) for the treatment of advanced prostate cancer (PC). This comparison was performed either in terms of biochemical or oncological or safety profiles. To this end we, carried out a systematic review and meta-analysis of the literature.We selected only studies directly and prospectively analyzing the two treatments in the same population (randomized phase III studies). We followed the Preferred Reporting Items for Systematic Reviews and meta-analyses process for reporting studies.After we eliminated studies according to the exclusion criteria, 9 publications were considered relevant to this review. These articles described 5 clinical trials that were eligible for inclusion. The follow-up duration in all trials did not exceed 364 days. This meta-analysis and review comprised a total of 1719 men, 1061 randomized to degarelix versus 658 to GnRH agonists treatment for advanced PC. Oncological results were evaluated only in 1 trial (CS21:408 cases) and they were not the primary endpoints of the study. Treatment emerging adverse events were reported in 61.4% and 58.8% of patients in the degarelix and GnRH agonists group, respectively (odds ratio, OR = 1.17; 95% confidence interval, 95% CI: 0.78-1.77, P > 0.1). Treatment related severe cardiovascular side effects were reported (trial CS21-30-35) in 1.6% and 3.6% of patients in the degarelix and GnRH agonists group, respectively (OR = 0.55, 95% CI: 0.26-1.14, P > 0.1).Our analysis evidences relevant limitations in particular for the comparative evaluation of the efficacy and the oncological results related to degarelix

Dissection of the gut microbiota in mothers and children with chronic Trichuris trichiura infection in Pemba Island, Tanzania

Background: Soil-transmitted helminthiases are important neglected tropical diseases that result in a notably high number of disability-adjusted life years worldwide. Characterizing the interactions between the human intestinal microbiome and helminths is of interest in the development of alternative treatments that do not rely on chemotherapeutics and do not lead to drug resistance.MethodsWe recruited and obtained fecal samples from 32 pairs of mothers and children on Pemba Island and monitored their intestinal microbiota using 16S rRNA gene sequencing.ResultsWe observed that microbial changes occur in the gut microbiota of infected mothers and children. Some short-chain fatty acid (SCFA)-producing bacteria and carbohydrate-degrading bacteria exhibited lower abundance in the infected individuals. Potentially pathogenic Campylobacter and proinflammatory Methanobrevibacter in infected mothers and opportunistic Enterococcus in infected children exhibited greater abundance.ConclusionsOur findings could reveal the microbiota profiling in T. trichiura-infected individuals, indicate the potential roles of key microbiota in the host and aid to the development of novel strategies to control T. trichiura infection

Nutrigenomics of Dietary Lipids

Dietary lipids have a major role in nutrition, not only for their fuel value, but also as essential and bioactive nutrients. This narrative review aims to describe the current evidence on nutrigenomic effects of dietary lipids. Firstly, the different chemical and biological properties of fatty acids contained both in plant- and animal-based food are illustrated. A description of lipid bioavailability, bioaccessibility, and lipotoxicity is provided, together with an overview of the modulatory role of lipids as pro- or anti-inflammatory agents. Current findings concerning the metabolic impact of lipids on gene expression, epigenome, and gut microbiome in animal and human studies are summarized. Finally, the effect of the individual’s genetic make-up on lipid metabolism is described. The main goal is to provide an overview about the interaction between dietary lipids and the genome, by identifying and discussing recent scientific evidence, recognizing strengths and weaknesses, to address future investigations and fill the gaps in the current knowledge on metabolic impact of dietary fats on health

The Interplay between Gut Microbiota and Parkinson's Disease: Implications on Diagnosis and Treatment

The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson's disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial and protective in several physiological processes, an excessive senescent cell burden has been involved in various pathological conditions including aging, tissue dysfunction and chronic diseases. Oxidative stress (OS) can drive senescence due to a loss of balance between pro-oxidant stimuli and antioxidant defences. Therefore, the identification and characterization of antioxidant compounds capable of preventing or counteracting the senescent phenotype is of major interest. However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking. Here, besides a brief description of the molecular mechanisms implicated in OS-mediated aging, we review and discuss the role of enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, minerals, flavonoids, and non-flavonoids as antioxidant compounds with an anti-aging potential, therefore offering insights into innovative lifespan-extending approaches

The Potential Role of Gut Microbiota in Alzheimer’s Disease: from Diagnosis to Treatment

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease characterized by amyloid-β (Aβ) plaque deposition and neurofibrillary tangle accumulation in the brain. Although several studies have been conducted to unravel the complex and interconnected pathophysiology of AD, clinical trial failure rates have been high, and no disease-modifying therapies are presently available. Fluid biomarker discovery for AD is a rapidly expanding field of research aimed at anticipating disease diagnosis and following disease progression over time. Currently, Aβ1−42, phosphorylated tau, and total tau levels in the cerebrospinal fluid are the best-studied fluid biomarkers for AD, but the need for novel, cheap, less-invasive, easily detectable, and more-accessible markers has recently led to the search for new blood-based molecules. However, despite considerable research activity, a comprehensive and up-to-date overview of the main blood-based biomarker candidates is still lacking. In this narrative review, we discuss the role of proteins, lipids, metabolites, oxidative-stress-related molecules, and cytokines as possible disease biomarkers. Furthermore, we highlight the potential of the emerging miRNAs and long non-coding RNAs (lncRNAs) as diagnostic tools, and we briefly present the role of vitamins and gut-microbiome-related molecules as novel candidates for AD detection and monitoring, thus offering new insights into the diagnosis and progression of this devastating disease

Population dynamics of microbiota bacteria lead morphogenetic variations, phenotypic pathogenesis shifts and antimicrobial resistance expression

The wide and essential role of the gut microbiota includes fending off pathogens, enabling nutrient generation, metabolism and absorption, participating in the development of immune and nervous system and more. Although correlational research has given us an insight on the microbiota composition, a mechanistic understanding of microbial population coordination and dynamics and its impact on the host health remains a key challenge. For example, the process that leads commensal microbiota players to become pathogens, and the factors that limit the establishment of incoming healthy bacteria (probiotics) have not been fully elucidated. Likewise, the critical involvement of micronutrients on microbial selection is at its infancy. The primary aim of this PhD Thesis was to investigate the differential prevalence of a subset of bacterial species commonly encountered in the gut as commensal or as pathogens to better understand bacterial population dynamics and competition. Specifically, we aimed to elucidate bacterial population dynamics in response to an underrated but emerging potential pathogen, Serratia marcescens, and external factors such as the micronutrient zinc. To study such a complex ecosystem, we used a bottom-up approach of in vitro co-culture competition experiments with pairs of bacterial species (Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella aerogenes, Staphylococcus aureus, Enterococcus faecalis, Lactobacillus plantarum and Streptococcus salivarius). A rich microbiological media was used as a surrogate for the postprandial intestine. While no difference in prevalence was observed in pairwise competitions between strains of E. coli and S. marcescens, we have identified a novel phenomenon where S. marcescens in co-culture with E. coli exhibited a differential spatial geometric distribution on solid media with the appearance of a “bull’s eye” pattern. The pattern only and consistently appeared in well-defined conditions (cell density, temperature, nutrients). This morphogenetic pattern was accompanied by phenotypic changes that affected virulence and antimicrobial resistance, a novel and cutting-edge finding that may help to design effective intervention tools to treat infectious diseases and tackle antibiotic resistance. The phenomenon was mathematically modelled, and the outcome suggested the need to increase model complexity thus informing biological research going forward. We also observed that P. aeruginosa prevailed over some Gram-positive cocci (S. aureus and S. streptococcus) and S. marcescens, and that Lactobacillus plantarum inhibited the growth of selected Gram-negatives. Our results established proof of concept regarding bacterial behaviours and morphogenetic variations that can be harnessed to explore genome-wide changes and related virulence and pathogenesis mechanisms, and may enrich the microbiota-linked prevention and infections management

Doxycycline, a role in the treatment of onchocerciasis-associated epilepsy?

Can the antibiotic doxycycline unlock new possibilities in the fight against onchocerciasis-associated epilepsy (OAE)? Idro et al. explored this question by investigating for the first time doxycycline's impact on nodding syndrome (NS), a severe manifestation of OAE. Results reveal significant findings that may shape future treatment strategies

Methods of assessment of zinc status in humans: an updated review and meta-analysis

Background: The assessment of zinc status is difficult, but vitally important for the identification of zinc deficiency and evaluation of interventions to improve zinc status. Objective: The purpose of this systematic review (SR) and meta-analysis was to update the previously published SR of biomarkers of zinc status, conducted by the European Micronutrient Recommendations Aligned (EURRECA) network in 2009, to answer the question: which putative measures (biomarkers) of zinc status appropriately reflect a change in zinc intake over a period of at least two weeks. Methods: A structured search strategy was used to identify articles published between January 2007 and September 2022 from MEDLINE (OVID), Embase (OVID), Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (CENTRAL). Relevant articles were identified using previously defined eligibility criteria. Data were extracted and combined with data from the previous SR. A random-effect model was used to calculate pooled mean differences using STATA. The risk of bias and the certainty of evidence for all outcomes were assessed. Results: Additional data on 7 of the 32 previously reported biomarkers were identified, along with data on an additional 40 putative biomarkers from studies published since 2007. Pooled data analysis confirmed that in healthy participants, both plasma/serum zinc concentration, and urinary zinc excretion responded to changes in zinc intake [plasma/serum: mean effect, (95% CI), controlled studies: 2.17 µmol/L (1.73, 2.61), p<0.005, I2 =97.8; before and after studies: 2.87 µmol/L (2.45, 3.30), p <0.005, I2=98.1%; urine zinc: 0.39 mmol/mol creatinine (0.17, 0.62), p<0.005, I2= 81.2; 3.09 µmol/d (0.16, 6.02), p=0.039, I2= 94.3]. Conclusions: The updated analyses support the conclusion that plasma/serum and urinary zinc respond to changes in zinc intake in studies of healthy participants. Several additional putative biomarkers were identified, but more studies are needed to assess the sensitivity and reliability