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A comprehensive characterization of the phytochemicals present in a blackberry fruit extract by HPLC-TOF-MS has been carried out. The main compounds in the extract were ursane-type terpenoids which, along with phenolic compounds, may be responsible for the bioactivity of the extract. In vitro antioxidant capacity was assessed through Folin–Ciocalteu (31.05 ± 4.9 mg GAE/g d.w.), FRAP (637.8 ± 3.2 μmol Fe2+/g d.w.), DPPH (IC50 97.1 ± 2.4 μg d.w./mL) and TEAC (576.6 ± 8.3 μmol TE/g d.w.) assays. Furthermore, the extract exerted remarkable effects on in vitro cellular antioxidant activity in HUVEC cells at a concentration of 5 mg/mL. Antimicrobial activity of the extract was also tested. Most sensible microorganisms were Gram-positive bacteria, such as E. faecalis, B. cereus and Gram-negative E. coli (MBC of 12.5 mg/mL). IC50 values against colon tumoral cells HT-29 (4.9 ± 0.2 mg/mL), T-84 (5.9 ± 0.3 mg/mL) and SW-837 (5.9 ± 0.2 mg/mL) were also obtained. Furthermore, blackberry extract demonstrated anti-inflammatory activity inhibiting the secretion of pro-inflammatory IL-8 cytokines in two cellular models (HT-29 and T-84) in a concentration-dependent manner. These results support that blackberry fruits are an interesting source of bioactive compounds that may be useful in the prevention and treatment of different diseases, mainly related to oxidative stress.

Fatigue and cognitive deficits are common and disabling symptoms in patients experiencing post-COVID condition. This randomized parallel study aimed to evaluate the effects of transcranial direct current stimulation (tDCS) over the primary motor cortex combined with cognitive training (M1 + CT), compared to tDCS over the dorsolateral prefrontal cortex with cognitive training (DLPFC + CT), on fatigue, cognition, and other clinical symptoms in post-COVID. Sixty-three patients completed the treatment (n = 32 in the M1 + CT group and n = 31 in the DLPFC + CT group) with a mean age of 47 years and an average symptom duration of 32 months. Both groups underwent comprehensive neuropsychological and clinical evaluations, including ecological momentary assessments of fatigue, at baseline, post-treatment, and one-month follow-up. The Fatigue Severity Scale (FSS) was used as the primary endpoint. Patients were randomly assigned to the M1 + CT or DLPFC + CT groups and received 15 sessions of tDCS administered concurrently with adaptive CT. The M1 + CT group showed a slightly higher efficacy in reducing fatigue and improving sleep quality than the DLPFC + CT group. Both groups demonstrated significant improvements in cognition, anxiety, depression, pain, and sleep quality. These improvements were sustained over time. These findings indicate that tDCS combined with cognitive training is a feasible, safe, and effective approach for reducing fatigue and enhancing cognition in post-COVID patients. The results highlight the potential of brain stimulation and cognitive training to alleviate fatigue and cognitive impairment in post-COVID, warranting further confirmation through additional randomized controlled trials. Trial registration: ClinicalTrials.gov NCT05753202.

Background Two main genetic risks for sporadic Alzheimer’s disease (AD) are a family history and ɛ4 allele of apolipoprotein E. The brain and retina are part of the central nervous system and share pathophysiological mechanisms in AD. Methods We performed a cross-sectional study with 30 participants without a family history of sporadic AD (FH−) and noncarriers of ApoE ɛ4 (ApoE ɛ4−) as a control group and 34 participants with a family history of sporadic AD (FH+) and carriers of at least one ɛ4 allele (ApoE ɛ4+). We analyzed the correlations between macular volumes of retinal layers and thickness of the peripapillary retinal nerve fiber layer (pRNFL) measured by optical coherence tomography (OCT) with the brain area parameters measured by magnetic resonance imaging (MRI) in participants at high genetic risk of developing AD (FH+ ApoE ɛ4+). Results We observed a significant volume reduction in the FH+ ApoE ɛ4+ group compared with the control group in some macular areas of (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL), (iii) inner nuclear layer (INL), and (iv) outer plexiform layer (OPL). Furthermore, in the FH+ ApoE ɛ4+ group, the retinal sectors that showed statistically significant volume decrease correlated with brain areas that are affected in the early stages of AD. In the same group, the peripapillary retinal nerve fiber layer (pRNFL) did not show statistically significant changes in thickness compared with the control group. However, correlations of these sectors with the brain areas involved in this disease were also found. Conclusions In cognitively healthy participants at high genetic risk of developing sporadic forms of AD, there are significant correlations between retinal changes and brain areas closely related to AD such as the entorhinal cortex, the lingual gyrus, and the hippocampus.

Vaccinium myrtillus L. (bilberry) leaves are an important by-product of berry production that may be used as a source of phenolic compounds which have a positive effect on human health. Therefore, an ultrasound-assisted extraction via sonotrode has been used for the first time to recover bioactive compounds from bilberry leaves. The extraction has been optimized using a Box–Behnken design. The influence of ethanol:water ratio (v/v), time of extraction (min) and amplitude (%) were evaluated considering total phenolic content (TPC) and antioxidant capacity (DPPH and FRAP assays) as dependent variables in a response surface methodology (RSM). Optimum values for the independent factors were 30:70 ethanol/water (v/v), 5 min of extraction and 55% amplitude. The empirical values of the independent variables using the optimized conditions were 217.03 ± 4.92 mg GAE/g d.w. (TPC), 271.13 ± 5.84 mg TE/g d.w. (DPPH) and 312.21 ± 9.30 mg TE/g d.w. (FRAP). The validity of the experimental design was confirmed using ANOVA and the optimal extract was characterized using HPLC-MS. A total of 53 compounds were tentatively identified, of which 22 were found in bilberry leaves for the first time. Among them, chlorogenic acid was the most abundant molecule, representing 53% of the total phenolic compounds identified. Additionally, the antimicrobial and anticancer activities of the optimum extract were tested. Gram-positive bacteria demonstrated high sensitivity to bilberry leaves extract in vitro, with MBC values of 6.25 mg/mL for Listeria monocytogenes, Listeria innocua and Enterococcus faecalis, and 0.8 mg/mL for Staphylococcus aureus and Bacillus cereus. Furthermore, bilberry leaves extract exerted in vitro antiproliferative activity against HT-29, T-84 and SW-837 colon tumor cells with IC50 values of 213.2 ± 2.5, 1140.3 ± 5.2 and 936.5 ± 4.6 μg/mL, respectively. Thus, this rapid ultrasound-assisted extraction method has demonstrated to be an efficient technique to obtain bilberry leaves extract with in vitro antioxidant, antimicrobial and anticancer capacities that may be useful for the food industry as natural preservative or even for the production of functional foods or nutraceuticals.

The revalorization of artichoke (Cynara scolymus L.) by-products is a promising strategy to obtain bioactive compounds with antioxidant properties, supporting a circular economy approach. This study compares the efficiency of an enzymatic pretreatment followed by microwave-assisted extraction (EMAE), ultrasound-assisted extraction (EUAE), and ultrasound-microwave-assisted extraction (EUMAE) at a pilot scale for recovering antioxidant compounds. Extracts were purified using Diaion® HP20 resin to obtain phenolic-rich fractions with enhanced antioxidant activity. The results showed that EUAE was the most effective technique, achieving a total phenolic content (TPC) of 210.76 ± 1.40 µmol GAE/g d.w. with an extraction yield of 21.38%. HPLC-MS analysis identified 14 major phenolic compounds, including chlorogenic acid isomers (60.73 mg/g d.e.), caffeic acid (34.29 mg/g d.e.), and luteolin rutinoside (103.27 mg/g d.e.), among others, which contribute to the extracts’ high bioactivity. The antioxidant potential of the extracts was assessed using Folin–Ciocalteu (F-C), ABTS, DPPH, and FRAP assays. EUAE extracts exhibited the highest antioxidant activity values, with F-C: 985.33 ± 4.46 µmol GAE/g d.e., ABTS: 80.46 ± 2.39 µmol TE/g d.e., DPPH: 87.03 ± 1.11 µmol TE/g d.e., and FRAP: 184.99 ± 2.52 µmol TE/g d.e. The purification process using Diaion® HP20 resin further enhanced TPC and antioxidant activity, with the enzyme–ultrasound-assisted extraction—purified extract (EUAE-PE) reaching a phenolic purity of 50.71% and an F-C value of 2981.35 ± 12.16 µmol GAE/g d.e.

BackgroundOver the past decade, the great impact of agricultural crop diseases has generated considerable economic losses and has compromised the production of edible crops at a time when the world population is only expected to rise, leading to the search for new pest management strategies. Besides that, the environmental impact resulting from the continued use of chemical pesticides has led to the search for natural and sustainable alternatives. One of the existing solutions that currently stands out for its effectiveness is the use of bioactive plant extracts. This study aims to evaluate the antimicrobial activity of propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO), two organosulfur compounds (OSCs) derived from Allium cepa, against a wide range of target bacteria and fungi. To this end, various in vitro procedures were conducted as well as soil sanitization tests using sterile substrate inoculated with soil-borne pathogens. In addition, this study also evaluates the pesticidal activity of both compounds through in vitro mortality and repellence tests.ResultsPTS and PTSO revealed inhibition activity on all the pathogens tested, belonging to different taxonomic groups. Moreover, both significatively reduced the population of bacteria and fungi in soil. The quantification of active substances in soil carried out in parallel to the microbial quantification showed that their use reduces the risk of residue accumulation since they break down quickly when applied. The set of antimicrobial tests performed demonstrated that the antifungal effect of both compounds is higher than the bactericidal effect. Lastly, PTS and PTSO showed a concentration-dependent significant biocidal and repellent effect against aphids.ConclusionsThe results presented in this work demonstrate that both PTS and PTSO have a significant antimicrobial and pesticidal activity against the great majority of phytopathogens tested, being a promising tool to improve pest management in crops.

The consumption of raw or smoked fish entails significant microbiological risks, including contamination by pathogens such as Listeria monocytogenes, which can cause severe foodborne illnesses. This study explores the preservative use of piscicolin CM22, a novel bacteriocin derived from the psychrotolerant strain Carnobacterium maltaromaticum CM22, in two types of edible coatings (EC): chitosan-based and fish gelatin-based. An initial in vitro characterization of the technological and antimicrobial properties of these ECs with and without bacteriocin was conducted. The efficacy of the edible coatings was subsequently evaluated through shelf life and challenge tests against L. monocytogenes in raw and smoked fish products. The results demonstrated significant antimicrobial activity, with the chitosan-based coating containing piscicolin CM22 being the most effective in reducing microbial counts and maintaining pH and color stability. Furthermore, in the challenge test studies, both ECs effectively controlled L. monocytogenes, showing significant reductions in bacterial counts compared to the controls in fresh tuna, salmon, and smoked salmon. The ECs containing piscicolin CM22 reduced Listeria counts by up to 4 log CFU/g in raw and smoked fish samples, with effective control in smoked salmon for up to 15 days at refrigeration temperature. While further research is required to fully assess their preservation potential, these findings strongly indicate that piscicolin CM22-functionalized edible coatings hold significant potential for improving the quality and safety of fish products.

The optimization of bioactive compound extraction from Fucus vesiculosus using ultrasound-assisted extraction (UAE) via sonotrode was investigated to maximize phenolic recovery and antioxidant activity while promoting a sustainable process. Optimal conditions (40% v/v ethanol in water, 38 min, 36% amplitude) were selected to maximize phenolic recovery while considering environmental and energy sustainability by optimizing extraction efficiency and minimizing solvent and energy usage. HPLC-ESI-QTOF-MS analysis tentatively identified 25 phenolic compounds, including sulfated phenolic acids, phlorotannins, flavonoids, and halophenols, with some reported for the first time in F. vesiculosus, underscoring the complexity of this alga’s metabolome. The antioxidant activity of the optimized extract was evaluated through FRAP (143.7 µmol TE/g), DPPH (EC50 105.6 µg/mL), and TEAC (189.1 µmol Trolox/g) assays. The optimized process highlights F. vesiculosus as a valuable source of natural antioxidants, with potential applications in biotechnology, cosmetics, and food industries.

Patients with post-COVID condition (PCC) present with diverse symptoms which persist at long-term after SARS-CoV-2 infection. Among these symptoms, cognitive impairment is one of the most prevalent and has been related to brain structural and functional changes. The underlying mechanisms of these cognitive and brain alterations remain elusive but neuroinflammation and immune mechanisms have been majorly considered. In this sense, the choroid plexus (ChP) volume has been proposed as a marker of neuroinflammation in immune-mediated conditions and the ChP epithelium has been found particularly susceptible to the effects of SARS-CoV-2. The objective was to investigate the ChP in PCC and evaluate its relationships with cognition, brain, and immunological alterations. One-hundred and twenty-nine patients with PCC after a mean of 14.79 ± 7.17 months of evolution since the infection and 36 healthy controls were recruited. Participants underwent a neuropsychological, and neuroimaging assessment and immunological markers evaluation. Results revealed ChP volume enlargement in PCC compared to healthy controls. The ChP enlargement was associated with cognitive dysfunction, grey matter volume reduction in frontal and subcortical areas, white matter integrity and diffusivity changes and functional connectivity changes. These ChP changes were also related to intermediate monocytes levels. Findings suggest that the ChP integrity may play a relevant role in the pathophysiology of cognitive deficits and the observed brain changes in PCC. The previously documented function of the ChP in maintaining brain homeostasis and regulating the entry of immune cells into the brain supports the presence of neuroinflammatory mechanisms in this disorder.

Propyl-propane thiosulfinate (PTS) and propyl-propane thiosulfonate (PTSO) are two volatile compounds derived from Allium cepa with a widely documented antimicrobial activity. The aim of this study was to evaluate their anti-candidiasis activity and the ability of its gaseous phase to inhibit bacterial and yeast growth in vitro. The minimum inhibitory concentration of various antifungal products (including PTS and PTSO) was determined versus 203 clinical isolates of Candida spp. through broth microdilution assay. Additionally, the antimicrobial activity through aerial diffusion of PTS and PTSO was evaluated over the growth of a collection of bacteria and yeasts cultivated in agar plates. All yeasts were susceptible to the antifungals tested, except C. glabrata and C. krusei, that showed azole resistance. PTSO (MIC50 and MIC90 ranged from 4 to 16 mg/L and 8 to 32 mg/L, respectively) was significantly more active against yeasts than PTS (MIC50 and MIC90 ranged from 16 to 64 mg/L and 32 to 64 mg/L). Values were higher than those obtained for antifungal drugs. Gaseous phases of PTS and PTSO generated growth inhibition zones whose diameters were directly related to the substances concentration and inversely related to the microbial inoculum. The quantification of PTS and PTSO levels reached in the growth media through aerial diffusion displayed a concentration gradient from the central zone to the periphery. Only P. aeruginosa ATCC 27853 showed resistance, while yeasts (C. albicans ATCC 200955 and C. krusei ATCC 6258) presented the higher susceptibility to both compounds. These results suggest that PTS and PTSO display antibacterial and anti-candidiasis activity in vitro through aerial diffusion, having potential use in human therapy.