A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

Preliminary Data on Gastrointestinal Deficiencies Incidence and the Prevalence of Anxiety During the COVID-19 Pandemic Among the Medical Workers.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious new ß-coronavirus that primarily affects the lungs. Because of its unprecedented spread, in a relatively short interval, it is declared a global pandemic. Binding to the angiotensin-converting enzyme 2 receptors, SARS-CoV-2 is easily disseminated through air. Apart from the established clinical panel, individuals exposed to prolonged chronic stress also manifest gastrointestinal (GI) symptoms similar to those exhibited by SARS-CoV-2-infected patients.The present study aims to assess the incidence of GI deficiencies and prevalence of anxiety among healthy medical staff by applying the Visual Analog Scale for Irritable Bowel Syndrome (VAS-IBS) and Hamilton Anxiety Rating Scale (HAM-A) during this global crisis.We found significant differences on several items of the VAS-IBS: regarding the incidence of diarrhea (p = 0.04), bloating/gases (p = 0.02), and nausea/vomiting (p = 0.01) from the physical spectrum. After stratification based on age of the participants and after we applied Kruskal-Wallis test because of heterogeneity between groups, we noted two situations in which the null hypothesis is rejected: nausea/vomiting in women between 20 and 30 years, and between 30 and 40, and between 40 and 50 years, respectively (p = 0.026/0.029). Anxiety was prevalent among young and middle-class people after the centralization of HAM-A data, where 40.4% of the participants had various forms of anxiety: mild (n = 13; 13.82%), severe (n = 13; 13.82%), and moderate (n = 12; 12.76%).This study demonstrates that VAS-IBS is a reliable tool for assessing the incidence of GI deficiencies, as well as HAM-A for anxiety.

Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia.

Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host's eubiosis. Based on combinations of specific keywords, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) for the established interval (2018-2022) and identified twenty two eligible cases, restricted only to human patients' experiences. Up until the writing of this manuscript, it has been revealed that the administration of specific lactic acid bacteria strains (Lactobacillus and Bifidobacterium), or those combined with vitamin D and selenium, maintain the integrity of the gut flora, preventing antagonistic effects including inflammation, antipsychotic-related body weight gain (olanzapine) and other metabolic dysfunctionalities. However, there are multiple antipsychotics that exert a potent effect upon gut flora, influencing a plethora of pathways and creating a dysbalance ratio between beneficial and opportunistic pathogens. Risperidone, amisulpride, and clozapine are just a few examples, but the current literature is unfortunately inconsistent and reported data is contradictory, which is why we support additional studies in this context. Moreover, we further argue the utility of studying how distinct controlled substances influence microbial communities, considering that ketamine is proved to alleviate depressive-like behavior as opposed to amphetamine and phencyclidine, which are known substances to trigger SCZ-like symptoms in experimental models. Probiotics may be regarded as the most consequential vehicle through which the gut flora can be successfully influenced, in adequate doses exerting a beneficial role as an alternative approach to alleviate SCZ symptoms.

Assessing Anti-Social and Aggressive Behavior in a Zebrafish (Danio rerio) Model of Parkinson's Disease Chronically Exposed to Rotenone.

Background: Rotenone (ROT) is currently being used in various research fields, especially neuroscience. Separated from other neurotoxins, ROT induces a Parkinson's disease (PD)-related phenotype that mimics the associated clinical spectrum by directly entering the central nervous system (CNS). It easily crosses through the blood−brain barrier (BBB) and accumulates in mitochondria. Unfortunately, most of the existing data focus on locomotion. This is why the present study aimed to bring novel evidence on how ROT alone or in combination with different potential ant(agonists) might influence the social and aggressive behavior using the counterclockwise rotation as a neurological pointer. Material and Methods: Thus, we exposed zebrafish to ROT­2.5 µg/L, valproic acid (VPA)­0.5 mg/mL, anti-parkinsonian drugs (LEV/CARB)­250 mg + 25 mg, and probiotics (PROBIO)­3 g for 32 days by assessing the anti-social profile and mirror tests and counterclockwise rotation every 4 days to avoid chronic stress. Results: We observed an abnormal pattern in the counterclockwise rotation only in the (a) CONTROL, (c) LEV/CARB, and (d) PROBIO groups, from both the top and side views, this indicating a reaction to medication and supplements administered or a normal intrinsic feature due to high levels of stress/anxiety (p < 0.05). Four out of eight studied groups­(b) VPA, (c) LEV/CARB, (e) ROT, and (f) ROT + VPA­displayed an impaired, often antithetical behavior demonstrated by long periods of time on distinct days spent on the right and the central arm (p < 0.05, 0.005, and 0.0005). Interestingly, groups (d) PROBIO, (g) ROT + LEV/CARB, and (h) ROT + PROBIO registered fluctuations but not significant ones in contrast with the above groups (p > 0.05). Except for groups (a) CONTROL and (d) PROBIO, where a normalized trend in terms of behavior was noted, the rest of the experimental groups exhibited exacerbated levels of aggression (p < 0.05, 0.005, and 0.001) not only near the mirror but as an overall reaction (p < 0.05, 0.005, and 0.001). Conclusions: The (d) PROBIO group showed a significant improvement compared with (b) VPA, (c) LEV/CARB, and ROT-treated zebrafish (e−h). Independently of the aggressive-like reactions and fluctuations among the testing day(s) and groups, ROT disrupted the social behavior, while VPA promoted a specific typology in contrast with LEV/CARB.

Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains.

Parkinson's disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa - LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio.

The Possible Role of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 on Locomotor Activity and Oxidative Stress in a Rotenone-Induced Zebrafish Model of Parkinson's Disease.

BACKGROUND: As every organ within the body, the brain is also extremely susceptible to a plethora of noxious agents that change its chemistry. One component frequently found in current products against harmful species to crops is rotenone whose effect under prolonged exposure has been demonstrated to cause neurodegenerative disorders such as Parkinson's disease. The latest reports have indeed revealed that rotenone promotes Parkinson's in humans, but studies aiming to show congruent effects in zebrafish (Danio rerio) are lacking. Material and Methods. In this context, the aim of the present study was to demonstrate how chronic administration of rotenone for 3 weeks impairs the locomotor activity and sociability and induces oxidative stress in zebrafish. RESULTS: There were no statistically significant differences following the analysis of their social interaction and locomotor tests (p > 0.05). However, several exceptions have been noted in the control, rotenone, and probiotics groups when we compared their locomotor activity during the pretreatment and treatment interval (p < 0.05). We further assessed the role of rotenone in disturbing the detoxifying system as represented by three enzymes known as superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Despite the fact that there were no statistically significant changes within SOD and GPx levels between the control group and rotenone, probiotics, and rotenone + probiotics (p > 0.05), relevant changes have been observed between the analyzed groups (p < 0.05 and p < 0.005, respectively). On the other hand, significant differences (p < 0.05) have been observed for MDA when we analyzed the data between the control group and the other three groups. CONCLUSIONS: Our results suggest that rotenone can be successfully used to trigger Parkinson's disease-related symptomatology in zebrafish.