Functional Alteration of Cerebello-Cerebral Coupling in an Experimental Mouse Model of Parkinson's Disease.

In Parkinson's disease, the degeneration of the midbrain dopaminergic neurons is consistently associated with modified metabolic activity in the cerebellum. Here we examined the functional reorganization taking place in the cerebello-cerebral circuit in a murine model of Parkinson's disease with 6-OHDA lesion of midbrain dopaminergic neurons. Cerebellar optogenetic stimulations evoked similar movements in control and lesioned mice, suggesting a normal coupling of cerebellum to the motor effectors after the lesion. In freely moving animals, the firing rate in the primary motor cortex was decreased after the lesion, while cerebellar nuclei neurons showed an increased firing rate. This increase may result from reduced inhibitory Purkinje cells inputs, since a population of slow and irregular Purkinje cells was observed in the cerebellar hemispheres of lesioned animals. Moreover, cerebellar stimulations generated smaller electrocortical responses in the motor cortex of lesioned animals suggesting a weaker cerebello-cerebral coupling. Overall these results indicate the presence of functional changes in the cerebello-cerebral circuit, but their ability to correct cortical dysfunction may be limited due to functional uncoupling between the cerebellum and cerebral cortex.

Walnut (Juglans regia L.) Septum: Assessment of Bioactive Molecules and In Vitro Biological Effects.

Walnut (Juglans regia L.) septum represents an interesting bioactive compound source by-product. In our study, a rich phenolic walnut septum extract, previously selected, was further examined. The tocopherol content determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed higher amounts of α-tocopherol compared to γ- and δ-tocopherols. Moreover, several biological activities were investigated. The in vitro inhibiting assessment against acetylcholinesterase, α-glucosidase, or lipase attested a real management potential in diabetes or obesity. The extract demonstrated very strong antimicrobial potential against Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella enteritidis. It also revealed moderate (36.08%) and strong (43.27%) antimutagenic inhibitory effects against TA 98 and TA 100 strains. The cytotoxicity of the extract was assessed on cancerous (A549, T47D-KBluc, MCF-7) and normal (human gingival fibroblasts (HGF)) cell lines. Flow cytometry measurements confirmed the cytotoxicity of the extract in the cancerous cell lines. Additionally, the extract demonstrated antioxidant activity on all four cell types, as well as anti-inflammatory activity by lowering the inflammatory cytokines (interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 ß (IL-1ß)) evaluated in HGF cells. To the best of our knowledge, most of the cellular model analyses were performed for the first time in this matrix. The results prove that walnut septum may be a potential phytochemical source for pharmaceutical and food industry.

Heterozygous Gnal Mice Are a Novel Animal Model with Which to Study Dystonia Pathophysiology.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions and its pathophysiological mechanisms are still poorly understood. Dominant mutations of the GNAL gene are a cause of isolated dystonia (DYT25) in patients. Some mutations result in a complete loss of function of the encoded protein, Gαolf, an adenylyl-cyclase-stimulatory G-protein highly enriched in striatal projection neurons, where it mediates the actions of dopamine and adenosine. We used male and female heterozygous Gnal knock-out mice (Gnal+/-) to study how GNAL haplodeficiency is implicated in dystonia. In basal conditions, no overt dystonic movements or postures or change in locomotor activity were observed. However, Gnal haploinsufficiency altered self-grooming, motor coordination, and apparent motivation in operant conditioning, as well as spine morphology and phospho-CaMKIIß in the striatum. After systemic administration of oxotremorine, an unselective cholinergic agonist, Gnal+/- mice developed more abnormal postures and movements than WT mice. These effects were not caused by seizures as indicated by EEG recordings. They were prevented by the M1-preferring muscarinic antagonists, telenzepine, pirenzepine, and trihexyphenidyl, which alleviate dystonic symptoms in patients. The motor defects were worsened by mecamylamine, a selective nicotinic antagonist. These oxotremorine-induced abnormalities in Gnal+/- mice were replicated by oxotremorine infusion into the striatum, but not into the cerebellum, indicating that defects in striatal neurons favor the appearance of dystonia-like movement alterations after oxotremorine. Untreated and oxotremorine-treated Gnal+/- mice provide a model of presymptomic and symptomatic stages of DYT25-associated dystonia, respectively, and clues about the mechanisms underlying dystonia pathogenesis.SIGNIFICANCE STATEMENT Adult-onset dystonia DYT25 is caused by dominant loss-of-function mutations of GNAL, a gene encoding the stimulatory G-protein Gαolf, which is critical for activation of the cAMP pathway in the striatal projection neurons. Here, we demonstrate that Gnal-haplodeficient mice have a mild neurological phenotype and display vulnerability to developing dystonic movements after systemic or intrastriatal injection of the cholinergic agonist oxotremorine. Therefore, impairment of the cAMP pathway in association with an increased cholinergic tone creates alterations in striatal neuron functions that can promote the onset of dystonia. Our results also provide evidence that untreated and oxotremorine-treated Gnal-haplodeficient mice are powerful models with which to study presymptomic and symptomatic stages of DYT25-associated dystonia, respectively.

Process Optimization for Improved Phenolic Compounds Recovery from Walnut (Juglans regia L.) Septum: Phytochemical Profile and Biological Activities.

Plant by-products can be valuable sources of polyphenol bioactive compounds. Walnut (Juglans regia L.) is a very important tree nut rich in biologically active molecules, but its septum was scarcely researched. Experimental data indicated a hypoglycemic effect of septum extracts, with almost no details about its phytochemical composition. The main objectives of this study were: (1) to obtain walnut septum (WS) extracts with high content in bioactive compounds and antioxidant activity based on an original experimental design; (2) characterization of the phytochemical profile of the WS extracts using HPLC-MS/MS; (3) evaluation of the biological potential of the richest polyphenolic WS extract. The variables of the experimental design were: extraction method (maceration and Ultra-Turrax extraction), temperature, solvent (acetone and ethanol), and percentage of water in the solvent. The first quantifiable responses were: total phenolic content, total flavonoid content, condensed tannins, and ABTS antioxidant capacity. The phytochemical profile of lyophilized extracts obtained by Ultra-Turrax extraction (UTE), the most efficient method, was further determined by HPLC-MS/MS analysis of individual polyphenolic and phytosterols compounds. It is the first study to assay the detailed composition of WS in hydrophilic and lipophilic compounds. The biological potential of the richest polyphenolic WS extract was also evaluated by FRAP and DPPH antioxidant capacity and the inhibition of tyrosinase, an enzyme involved in the browning in fruits and vegetables, skin wrinkles and aging. Conclusion: The phytochemical profile of the analyzed extracts proves that WS can be a valuable source of biologically active compounds (polyphenols) for food and/or pharmaceutical industry and warrant the continuation of current research in further evaluating its bioactive potential.

Inhibitory Effect of Citalopram on the Pharmacokinetics of Carvedilol in Rats and in vitro Models.

BACKGROUND/AIMS: The aim of this study was to investigate the drug-drug interaction between carvedilol and citalopram based on carvedilol metabolism in vitro and his pharmacokinetics (PKs) in vivo after the oral administration of the single drug and both drugs, and reveal citalopram effects on the PKs of carvedilol. METHODS: Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body weight [b.w.]) in the absence of citalopram or after a pre-treatment with multiple oral doses of citalopram (1.42 mg/kg b.w.). Plasma concentrations of carvedilol were determined using high-performance liquid chromatography-MS at the designated time points after drug administration, and the main PK parameters were calculated by noncompartmental analysis. In addition, effects of citalopram on the metabolic rate of carvedilol were investigated using rat-pooled liver microsome incubation systems. RESULTS: During co-administration, significant increases of the area under the plasma concentration-time curve as well as of the peak plasma concentration were observed. The rat-pooled liver microsome incubation experiment indicated that citalopram could decrease the metabolic rate of carvedilol. CONCLUSION: Citalopram co-administration led to a significant alteration of carvedilol's PK profile in rats; it also demonstrated, in vitro, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition.

Patients' perceptions of healthcare professionalism-a Romanian experience.

BACKGROUND: The main objective of this cross sectional study was to assess the psychometric properties of a new research instrument. The secondary aim was to analyze patients' levels of dissatisfaction with the professionalism of medical staff. METHODS: A social survey questionnaire was created and administered online. The instrument consisted of two scales: the 30-item patient dissatisfaction scale and the 10 items institutional scale. In this article, we assessed only the patient dissatisfaction scale. The research population includes 1838 subjects. The statistical procedures used were descriptive statistics, Pearson's correlation, and factorial analyses with the SPSS.19 software. The internal consistency of the instrument was determined using the Cronbach's alpha coefficient. We used a principal component analysis to investigate the factorial validity of the scale. RESULTS: The patients' scale of dissatisfaction obtained an alpha Cronbach score of 0.81. Three latent factors corresponding to three dimensions of dissatisfaction emerged from the data: medical staff's ability to communicate, medical staff's hygiene, as well as sanitary and privacy conditions within the hospital. The first factor explained 43.47% of the variance in patient dissatisfaction, the second factor explained 10.24%, and the third factor explained 7.59%; overall, the three factors explained 61.30% of the total variance. CONCLUSION: The Romanian healthcare system has an organization and management structure which has shown few changes since the communist period. Our study indicates that although more than 25 years have passed since the political regime changed in Romania and the introduction of a different system of social care, there have been no corresponding changes in the medical staff's mentality or in the way that patients are approached. The present assessment of patient dissatisfaction is not a strictly theoretical exercise; it also represents a valuable instrument for healthcare system management.

The Use of Lipid Peroxidation Expression as a Biomarker for the Molecular Damage in the Critically Ill Polytrauma Patient.

BACKGROUND: The critically ill polytrauma patient, apart from the primary, traumatic injuries and the secondary, port-traumatic injuries, presents with a series of molecular disasters. Dysfunctions of the biochemical pathways and molecular damage add to the worsening of the clinical status of these patients, one of the most well-known molecular phenomena being oxidative stress (OS), responsible for an escalation of the inflammatory status, multiple infections, and multiple organ dysfunction syndrome (MODS). METHODS: For this study was analysed the literature available on PubMed and Scopus. The key words used in the search were "oxidative stress", "lipid peroxidation", "critically ill", "polytrauma patients", and "biomarkers oxidative stress". RESULTS: For the study we selected 47 science articles. The oxidative attack on lipids is responsible for the biosynthesis of an increased quantity of free radicals (FR), which further intensifies and aggravates the redox status in these patients. CONCLUSIONS: One of the most aggressive redox mechanisms related to lipid molecules is known as lipid peroxidation (LPOX).

Acute toxicity evaluation of a thiazolo arene ruthenium (II) complex in rats.

Recently, a series of thiazolo arene ruthenium complexes were found to be highly cytotoxic in vitro, on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. The most active compound of the series, [(η(6)-p-cymene)Ru(L)Cl]Cl (L = 1-(2-(2-(3-chlorobenzylidene)hydrazinyl)-4-methylthiazol-5-yl)ethanone), was selected for an in vivo study in order to assess its safety profile. The ruthenium complex was administered to female Crl:WI rats orally, by gastric intubation and intraperitoneal injection. The hematological parameters and the histopathological changes in liver, kidneys, spleen and brain were investigated after a 14-days treatment. The substance was very well tolerated orally, with a LD50 value of over 2000 mg/kg body weight. Symptoms were observed only in the first day after intraperitoneal administration of the highest dose, with a LD50 value between 300 and 2000 mg/kg bw. The hematological profile was not modified at any of the tested doses, after both oral and intraperitoneal acute administration. Structural modifications (moderate lymphocytolysis) were identified only in the spleen at the highest tested dose. In conclusion, the thiazolo arene ruthenium complex was very well tolerated orally and had a low acute toxicity after intraperitoneal administration in Crl:WI rats The results justify further investigation to determine the in vivo therapeutic potential of this promising ruthenium complex.

Clusters of cerebellar Purkinje cells control their afferent climbing fiber discharge.

Climbing fibers, the projections from the inferior olive to the cerebellar cortex, carry sensorimotor error and clock signals that trigger motor learning by controlling cerebellar Purkinje cell synaptic plasticity and discharge. Purkinje cells target the deep cerebellar nuclei, which are the output of the cerebellum and include an inhibitory GABAergic projection to the inferior olive. This pathway identifies a potential closed loop in the olivo-cortico-nuclear network. Therefore, sets of Purkinje cells may phasically control their own climbing fiber afferents. Here, using in vitro and in vivo recordings, we describe a genetically modified mouse model that allows the specific optogenetic control of Purkinje cell discharge. Tetrode recordings in the cerebellar nuclei demonstrate that focal stimulations of Purkinje cells strongly inhibit spatially restricted sets of cerebellar nuclear neurons. Strikingly, such stimulations trigger delayed climbing-fiber input signals in the stimulated Purkinje cells. Therefore, our results demonstrate that Purkinje cells phasically control the discharge of their own olivary afferents and thus might participate in the regulation of cerebellar motor learning.

Functional role of the cerebellum in gamma-band synchronization of the sensory and motor cortices.

The cerebellum is an essential structure for the control of movement. It sends abundant ascending projections to the cerebral cortex via the thalamus, but its contribution to cortical activity remains largely unknown. Here we studied its influence on cortical neuronal activity in freely moving rats. We demonstrate an excitatory action of the cerebellum on the motor thalamus and the motor cortex. We also show that cerebellar inactivation disrupts the gamma-band coherence of local field potential between the sensory and motor cortices during whisking. In contrast, phase locking of neuronal activities to local gamma oscillations was preserved in the sensory and motor cortices by cerebellar inactivation. These results indicate that the cerebellum contributes to coordinated sensorimotor cortical activities during motor activation and thus participates in the multiregional cortical processing of information.

Amygdala intercalated neurons are required for expression of fear extinction.

Congruent findings from studies of fear learning in animals and humans indicate that research on the circuits mediating fear constitutes our best hope of understanding human anxiety disorders. In mammals, repeated presentations of a conditioned stimulus that was previously paired to a noxious stimulus leads to the gradual disappearance of conditioned fear responses. Although much evidence suggests that this extinction process depends on plastic events in the amygdala, the underlying mechanisms remain unclear. Intercalated (ITC) amygdala neurons constitute probable mediators of extinction because they receive information about the conditioned stimulus from the basolateral amygdala (BLA), and contribute inhibitory projections to the central nucleus (CEA), the main output station of the amygdala for conditioned fear responses. Thus, after extinction training, ITC cells could reduce the impact of conditioned-stimulus-related BLA inputs to the CEA by means of feed-forward inhibition. Here we test the hypothesis that ITC neurons mediate extinction by lesioning them with a toxin that selectively targets cells expressing micro-opioid receptors (microORs). Electron microscopic observations revealed that the incidence of microOR-immunoreactive synapses is much higher in ITC cell clusters than in the BLA or CEA and that microORs typically have a post-synaptic location in ITC cells. In keeping with this, bilateral infusions of the microOR agonist dermorphin conjugated to the toxin saporin in the vicinity of ITC neurons caused a 34% reduction in the number of ITC cells but no significant cell loss in surrounding nuclei. Moreover, ITC lesions caused a marked deficit in the expression of extinction that correlated negatively with the number of surviving ITC neurons but not CEA cells. Because ITC cells exhibit an unusual pattern of receptor expression, these findings open new avenues for the treatment of anxiety disorders.

Influence of Genista tinctoria L. or methylparaben on subchronic toxicity of bisphenol A in rats.

OBJECTIVE: To evaluate the influence of an extract of Genista tinctoria L. herba (GT) or methylparaben (MP) on histopathological changes and 2 biomarkers of oxidative stress in rats subchronicly exposed to bisphenol A (BPA). METHODS: Adult female Wistar rats were orally exposed for 90 d to BPA (50 mg/kg), BPA+GT (35 mg isoflavones/kg) or BPA+MP (250 mg/kg). Plasma and tissue samples were taken from liver, kidney, thyroid, uterus, ovary, and mammary gland after 30, 60, and 90 d of exposure respectively. Lipid peroxidation and in vivo hydroxyl radical production were evaluated by histological analysis along with malondialdehyde and 2,3-dihydroxybenzoic acid detection. RESULTS: The severity of histopathological changes in liver and kidneys was lower after GT treatment than after BPA or BPA+MP treatment. A minimal thyroid receptor antagonist effect was only observed after BPA+MP treatment. The abnormal folliculogenesis increased in a time-dependent manner, and the number of corpus luteum decreased. No significant histological alterations were found in the uterus. The mammary gland displayed specific estrogen stimulation changes at all periods. Both MP and GT revealed antioxidant properties reducing lipid peroxidation and BPA-induced hydroxyl radical generation. CONCLUSION: GT L. extract ameliorates the toxic effects of BPA and is proved to have antioxidant potential and antitoxic effect. MP has antioxidant properties, but has either no effect or exacerbates the BPA-induced histopathological changes.

Do we develop public health leaders?- association between public health competencies and emotional intelligence: a cross-sectional study.

BACKGROUND: Professional development of public health leaders requires a form of instruction which is competency-based to help them develop the abilities to address complex and evolving demands of health care systems. Concurrently, emotional intelligence (EI) is a key to organisational success. Our aim was twofold: i) to assess the relationship between the level of self-assessed public health and EI competencies among Master of European Public Health (MEPH) students and graduates at Maastricht University, and; ii) to determine the relationship between different groups of public health competencies and specific EI skills. METHODS: A cross-sectional study was conducted including all recent MEPH graduates and students from 2009-2012, out of 67 eligible candidates N = 51 were contacted and N = 33 responded (11 males and 22 females; overall response: 64.7%).Two validated tools were employed: i) public health competencies self-assessment questionnaire, and; ii) Assessing Emotions Scale. RESULTS: Females scored higher than males in all seven domains of the self-assessed key public health competencies (NS) and emotional intelligence competences (P = 0.022). Overall, the mean value of public health competencies was the lowest in students with "staff" preferences and the highest among students with mixed job preferences (P < 0.001). There was evidence of a correlation between the overall public health competencies and the overall emotional intelligence competencies (r = 0.61, P < 0.001). CONCLUSIONS: The study shows a positive correlation between public health specific competencies and EI attributes. It can contribute to the improvement of the educational content of PH curricula by rising awareness through self-assessment and supporting the identification of further educational needs related to leadership.

Looking at the Data on Smoking and Post-COVID-19 Syndrome-A Literature Review.

Long COVID is a recently described entity that is responsible for significant morbidity and that has consequences ranging from mild to life-threatening. The underlying mechanisms are not completely understood, and treatment options are currently limited, as existing data focus more on risk factors and predictors. Smoking has been reported as a risk factor for poor outcomes of acute SARS-CoV-2 infection and seems to also play a role in mediating post-COVID-19 symptoms. We aimed to review relevant work addressing the interaction between smoking and long COVID in order to characterize smoking's role as a risk factor and possibly identify new research directions. Methods: The PubMed/MEDLINE database was searched using the keywords 'smoking', 'long COVID', and 'post-acute COVID' to identify relevant English-language articles published up to October 2023. Results and conclusions: From the 374 initial hits, a total of 36 papers were deemed relevant to the aim of the review. There was significant variability concerning the ways in which tobacco usage was quantified and reported; still, there is compelling evidence linking smoking to an increased risk of developing manifestations of post-acute-COVID disease. Some clinical conditions, such as dyspnea, cardiovascular symptoms, and cognitive or mental-health impairment, seem to be relatively strongly associated with smoking, while the connection between smoking and upper-airway involvement seems less certain. The available data support recommending smoking cessation as a clinical tool for the prevention of long COVID.

Microglial TNFα controls daily changes in synaptic GABAARs and sleep slow waves.

Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNFα. We demonstrate that sleep induces microglia-dependent synaptic enrichment of GABAARs in a manner dependent on microglial TNFα and P2RX7. We further show that microglia-specific depletion of TNFα alters slow waves during NREM sleep and blunt memory consolidation in sleep-dependent learning tasks. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs, sculpt sleep slow waves, and support memory consolidation.

Laboratory Diagnostics Accuracy for COVID-19 versus Post-COVID-19 Syndrome in Lung Disease Patients with Multimorbidity.

The laboratory tests and identification of risk factors such as comorbidities are essential in the management, treatment and prognosis of patients with chronic respiratory diseases. Performing rigorous monitoring among patients with post-COVID-19 syndrome and early identification of risk factors associated with poor prognosis are crucial in improving patient outcomes. In the present study, 182 patients diagnosed with COVID-19 and PCI during 2020-2022 were included. A clinical and epidemiological evaluation was performed for each patient. Laboratory tests at admission included complete blood count, Erythrocyte Sedimentation Rate (ESR) and biochemical tests. Receiver operating curve (ROC) and area under the curve (AUC) were calculated to compare the diagnostic performance of each parameter. Regarding comorbidities, arterial hypertension, diabetes mellitus and obesity were the most frequent ones. In the case of chronic lung diseases, asthma and Chronic Obstructive Pulmonary Disease (COPD) were the most frequent. Pleurisy was found especially in patients with PCI Variations in serum LDH values were observed, especially in severe forms of COVID-19 in 2020, with a mean value of 481.44 U/L, compared to patients with PCI, whose mean values (122 U/L) were within the biological range of reference. High neutrophil/lymphocyte ratio (NLR) values quantified in this study were especially associated with moderate and severe forms of COVID-19 and also PCI. The Spearman correlation coefficient was determined to measure the correlations between the clinical parameters of all investigated subjects. A value of p < 0.05 was considered statistically significant. The statistical results indicated that serum lactate dehydrogenase (LDH), glucose and C-reactive protein (CRP) are sensitive markers with a diagnostic role in COVID-19, and lymphocyte (Ly) count, CRP, ESR and glucose were evidenced to be target markers in PCI. LDH values were observed to be statistically significant (p < 0.005) in patients with COVID-19 and obesity evaluated in 2021, while Ly count was statistically significant (p = 0.05) in patients with PCI and arterial hypertension. Regarding comorbidities, it has been observed that obesity, arterial hypertension and cardiovascular diseases represent risk factors in COVID-19/PCI, associated especially with the severe forms of the disease.

Coherent amygdalocortical theta promotes fear memory consolidation during paradoxical sleep.

Brain activity in sleep plays a crucial role in memory consolidation, an offline process that determines the long-term strength of memory traces. Consolidation efficacy differs across individuals, but the brain activity dynamics underlying these differences remain unknown. Here, we studied how interindividual variability in fear memory consolidation relates to neural activity in brain structures that participate in Pavlovian fear learning. From the end of training to testing 24 h later, some rats showed increased and others decreased conditioned fear responses. We found that overnight bidirectional changes in fear memory were selectively correlated with modifications in theta coherence between the amygdala, medial prefrontal cortex, and hippocampus during paradoxical sleep. Thus, our results suggest that theta coordination in the limbic system may influence interindividual differences in memory consolidation of aversive experiences.

Phytochemicals and Biological Activities of Walnut Septum: A Systematic Review.

In the last few decades, scientific evidence has stressed the importance of plants in the prevention and/or supportive treatment of a plethora of diseases, many of them chronic, age-associated disorders. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. Due to the presence of biologically active compounds, walnut was used in the treatment of various maladies. Recently, investigations have focused on the walnut by-products and waste products, with research on their valuable constituents and active properties. Among these secondary products, walnut septum was analyzed in several studies, its phytochemical profile described, and some of the biological activities examined. However, compared to other walnut by-products, no comprehensive review to gather all the pertinent scientific knowledge was found in the literature. Therefore, the aim of this study was to critically assess the information furnished by peer-reviewed articles regarding the walnut septum chemical composition and the related biological activities, including antioxidant activities, anti-inflammatory effects, antimicrobial properties, antidiabetic activities, anti-tumor properties, and anti-aging potential. In conclusion, as these preclinical studies showed that walnut septum metabolites were responsible for a wide range of preventive and therapeutic uses, further research should confirm the beneficial outcomes in clinical trials.

The Impact of Ellagitannins and Their Metabolites through Gut Microbiome on the Gut Health and Brain Wellness within the Gut-Brain Axis.

Ellagitannins (ETs) are a large group of bioactive compounds found in plant-source foods, such as pomegranates, berries, and nuts. The consumption of ETs has often been associated with positive effects on many pathologies, including cardiovascular diseases, neurodegenerative syndromes, and cancer. Although multiple biological activities (antioxidant, anti-inflammatory, chemopreventive) have been discussed for ETs, their limited bioavailability prevents reaching significant concentrations in systemic circulation. Instead, urolithins, ET gut microbiota-derived metabolites, are better absorbed and could be the bioactive molecules responsible for the antioxidant and anti-inflammatory activities or anti-tumor cell progression. In this review, we examined the dietary sources, metabolism, and bioavailability of ETs, and analyzed the last recent findings on ETs, ellagic acid, and urolithins, their intestinal and brain activities, the potential mechanisms of action, and the connection between the ET microbiota metabolism and the consequences detected on the gut-brain axis. The current in vitro, in vivo, and clinical studies indicate that ET-rich foods, individual gut microbiomes, or urolithin types could modulate signaling pathways and promote beneficial health effects. A better understanding of the role of these metabolites in disease pathogenesis may assist in the prevention or treatment of pathologies targeting the gut-brain axis.

Phytochemical Profiling and Biological Activities of Quercus sp. Galls (Oak Galls): A Systematic Review of Studies Published in the Last 5 Years.

Quercus species have been widely used in traditional medicine, and recently, researchers' attention has focused on galls of the genus Quercus as a source of health-promoting phytochemicals. This review presents a summary of the most recent findings on the phytochemistry and bioactivity of oak galls, following the screening of scientific papers published in two relevant databases, PubMed and Embase, between January 2018 and June 2023. The oak galls are rich in active compounds, mostly gallotannins and phenolic acids. Due to these secondary metabolites, the reviewed studies have demonstrated a wide range of biological activities, including antioxidant and anti-inflammatory actions, antimicrobial properties, tissue-protective effects, and antitumor, anti-aging, and hypoglycemic potential. Thus, oak galls are a promising natural matrix, to be considered in obtaining pharmaceutical and cosmetic preparations used in anti-aging strategies and, together with medications, in the management of age-related diseases. In further evaluations, the valuable functional properties of oak galls, reported mostly in preclinical studies, should be confirmed with clinical studies that would also take into account the potential health risks of their use.