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Summary Selected plants used in Rwandan traditional medicine for the treatment of infections and/or rheumatoid diseases were investigated for antiviral activity in vitro against human immunodeficiency virus type-1 (HIV-1). Of [...]

Summary Forty-two ethanolic extracts of thirty-six Rwandan medicinal plants were investigated for their influence on complement-mediated hemolysis. The plants were selected on the base of their ethnomedicinal use in infections [...]

Maternal metabolic disorders linked to lipolysis are major risk factors for reproductive failure. A notable feature of such disorders is increased non-esterified fatty acid (NEFA) concentrations in the blood, which are reflected in the ovarian follicular fluid. Elevated NEFA concentrations impact on the maturing oocyte and even alter subsequent embryo physiology. The aetiological mechanisms have not been fully elucidated. Therefore, in the present study, bovine in vitro maturing cumulus-oocyte complexes were exposed (24 h) to three different maturation treatments containing: (1) physiological (72 µM) NEFA concentrations (= control); (2) elevated (75 µM) stearic acid (SA) concentrations (= HIGH SA); and (3) elevated (425 µM) NEFA concentrations (= HIGH COMBI). Zygotes were fertilised and cultured following standard procedures. Transcriptomic analyses in resulting Day 7.5 blastocysts revealed that the major pathways affected are related to lipid and carbohydrate metabolism in HIGH COMBI embryos and to lipid metabolism and cell death in HIGH SA embryos. Furthermore, lower glutathione content and a reduced number of lipid droplets per cell were observed in HIGH SA-exposed oocytes and resulting morulae, respectively, compared with their HIGH COMBI-exposed counterparts. Vitrified embryos originating from HIGH SA-exposed oocytes tended to exhibit lower survival rates compared with controls. These data suggest possible mechanisms explaining why females across species suffering lipolytic disorders experience difficulties in conceiving. Metabolic disorders are risk factors for reproductive failure and elevated non-esterified fatty acid (NEFA) concentrations have been proposed as key contributors by affecting oocyte quality. The aim of this study was to unravel the underlying molecular mechanisms through which NEFAs impact on bovine maturing oocytes and subsequent embryo development. Transcriptome and functional data point to metabolic dysregulation in the resulting preimplantation embryos, findings that might explain the reduced conception rates in females across species suffering lipolytic disorders. [ABSTRACT FROM AUTHOR]

AIM OF THE STUDY: Elaeodendron schlechteranum (Loes.) Loes. is a shrub or tree belonging to the family Celastraceae. In Tanzania, in addition to ethnopharmacological claims in treating various non-infectious diseases, the root and stem bark powder is applied on septic wounds, and the leaf paste is used for treatment of boils and carbuncles. The aim of this study was to identify the putative active constituents of the plant. MATERIALS AND METHODS: Dried and powdered root bark was extracted and subjected to bioassay-guided fractionation, based on antibacterial, antiparasitic and anti-HIV activity. Isolated compounds were identified by spectroscopic methods, and evaluated for biological activity. RESULTS AND CONCLUSIONS: Bioassay-guided isolation led to the identification of tingenin B (22beta-hydroxytingenone) as the main antibacterial constituent. It was active against Bacillus cereus, Staphylococcus aureus and Escherichia coli (IC(50)<0.25 microg/mL). Furthermore, antiparasitic activity was observed against Trypanosoma cruzi (IC(50)<0.25 microg/mL), Trypanosoma brucei (<0.25 microg/mL), Leishmania infantum (0.51 microg/mL), and Plasmodium falciparum (0.36 microg/mL). Tingenin B was highly cytotoxic to MRC-5 cells (CC(50) 0.45 microg/mL), indicating a poor selectivity. Two inactive triterpenes, 3beta,29-dihydroxyglutin-5-ene and cangoronine methyl ester were also obtained. Phytochemical investigation of the anti-HIV active fractions led to the isolation and identification of three phenolic compounds, namely 4'-O-methylepigallocatechin, 4'-O-methylgallocatechin, and a new procyanidin dimer, i.e. 4',4'''-di-O-methyl-prodelphinidin B(4) or 4'-O-methylgallocatechin-(4alpha-->8)-4'-O-methylepigallocatech in. However, none of these showed anti-HIV activity. [ABSTRACT FROM AUTHOR]

Graphite furnace atomic absorption spectrometry, with Zeeman background correction and improved matrix modification, was used to measure the plasma selenium content of healthy blood bank donors at the sea-side part of Belgium. The mean plasma selenium concentration of 100 men and 100 women was 79.3 ± 11.0 ng/ml with a range of 51.9 - 117.7 ng/ml. Women tended to have lower selenium levels compared to men, but at a statistically insignificant level (p > 0.05). No effect of age was observed. The mean plasma selenium concentration measured corresponded well with literature data for Belgium. The obtained values were found to be in the medium range, compared with recent literature values for the European countries. Some factors, influencing concentration levels, are discussed. [ABSTRACT FROM AUTHOR]

Daily dietary sodium (Na) and potassium (K) intake in healthy toddlers in the Antwerp region of Belgium, aged 2 - 3 years, have been evaluated by duplicate portion sampling. The elemental content was analyzed by atomic absorption spectrometry after acid destruction and heating in a microwave oven. Mean sodium intake (2,381 ± 694 mg/d) was very high compared with and far above the population reference intake (PRI) for Belgium or the recommended dietary allowance (RDA) value (330 mg/d). For potassium, mean intake (2,563 ± 567 mg/d) was higher than in most other countries and 2.5 times more than the PRI range for Belgium (800- 1,000). The intake of Na and K by the healthy toddler population in the Antwerp region seems to be too high for both elements, especially for sodium. [ABSTRACT FROM AUTHOR]

A total of 45 Rwandan plant extracts, belonging to 37 different plant species out of 21 families, were investigated for their antibacterial, antifungal, and antiviral properties. The plants were selected on the base of their ethnomedicinal use against infections and autoimmune diseases. From all the plant extracts tested, only Clematis hirsuta (leaves) showed a pronounced antifungal activity against Candida albicans and the dermatophytes Trichophyton rubrum, Epidermophyton floccosum, and Microsporum canis. Seven plant extracts showed a high antiviral activity against the DNA-virus Herpes simplex type 1, while five and three plant extracts were highly active against the RNA-viruses Coxsackie and Polio, respectively. Only Macaranga kilimandscharica (leaves) showed an interesting anti-measles activity, whereas Eriosema montanum (leaves) and Entada abyssinica (leaves) were highly active against Semliki forest virus. Some plant extracts showed an antibacterial activity against Gram-positive bacteria and Mycobacterium fortuitum, but none of them were active against the Gram-negative bacteria tested. [Copyright &y& Elsevier]

Abstract: An aqueous decotion (dried extract), an 80% MeOH extract from Morinda morindoides leaves, and 10 flavonoids and 4 iridoids isolated from the 80% MeOH extract were evaluated in vitro for their potential antiamoebic activity and their cytotoxic effect against MT-4 cells. Results indicated that the aqueous decoction and the 80% MeOH extract exhibited an interesting antiamoebic activity with IC50 values of 3.1±1.7 and 1.7±0.6μg/ml, respectively. Apigenin-7-O-glucoside and luteolin-7-O-glucoside exhibited a moderate antiamoebic activity with IC50 values of 22.3±3.2 and 37.4±2.7μg/ml, respectively. Kaempferol (IC50 =10.3±2.3μg/ml), apigenin (IC50 =12.7±4.3μg/ml), and luteolin (IC50 =17.8±4.3μg/ml) showed a more pronounced activity than their corresponding glycosides. All tested iridoids displayed a very good activity with IC50 values less than 10μg/ml. The most active iridoids were epoxygaertneroside (IC50 =1.3±0.4μg/ml) and methoxygaertneroside (IC50 =2.3.±0.7), followed by gaertneroside and gaertneric acid with IC50 values of 4.3±1.8 and 7.1±1.4μg/ml, respectively. Except quercetin and quercetin-7,4′-dimethylether which have shown a cytotoxic effect with IC50 ranging from 14 to 22μg/ml. No correlation could be deduced between the observed antiamoebic and cytotoxic activity of these tested samples. A structure–activity relationship for isolated compounds is discussed. These findings support the medicinal report for the traditional use of Morinda morindoides leaves for the treatment of amoebiasis. [Copyright &y& Elsevier]

Abstract: The ethanolic extracts from fresh apical stems of Phyllanthus niruri L. (Euphorbiaceae) cultured on Murashige and Skoog (MS) medium supplemented with IBA/BAP/Coco nucifera L. milk for 1, 2, 4 and 6 months were phytochemically and biologically investigated and compared with intact plant part and whole plant extracts. Results from the in vitro antiplasmodial testing indicated that the EtOH extract of a 1-month-old callus culture (IC50 = 16.3 ± 2.5μg/ml) exhibited a higher activity than the ethanolic extracts of the fresh apical stem (IC50 = 18.2 ± 2.4μg/ml) and callus cultures of 2-, 4- and 6-months-old (25μg/ml &#60; IC50 &#60; 40μg/ml). These activities were however lower than that displayed by the ethanolic extract of the whole plant (IC50 &#60; 3μg/ml). The EtOH extract of 1-month-old callus culture (the most active) was fractionated with solvents of different polarities. Its CH2Cl2 fraction rich in terpenic constituents (IC50 = 9.2 ± 3.4μg/ml) exhibited a higher antiplasmodial activity than its isoamylic alcohol fraction obtained at pH 2–3 (IC50 = 25.6 ± 2.3μg/ml) rich in flavonoids. The activity of these two fractions was lower than that displayed by the same fractions from the whole plant (2μg/ml &#60; IC50 &#60; 3μg/ml). Alkaloidic fractions from the whole plant and 1-month-old callus culture of fresh apical stem were considered as inactive (IC50 > 100μg/ml). [Copyright &y& Elsevier]

The chemical composition of essential oils from 15 aromatic medicinal plant species growing in the Democratic Republic of Congo have been studied. More than 15 constituents in an amount higher than 0.1% were identified in each essential oil. 1,8-cineole, α and β-pinene, p-cymene, myrcene, γ-terpinene, α-terpineol and limonene were prevalent constituents in almost more than 10 selected plant species. Results from the antibacterial testing by the diffusion method indicate that all essential oils (5 μl per disc) inhibited the growth of selected bacteria at different extents. The most active antibacterial essential oils were those of the leaves of Eucalyptus camadulensis and Eucalyptus terticornis (12–30 mm zone diameter of inhibition). They showed particularly a most potent inhibition of Pseudomonas aeruginosa growth (15–16 mm), followed by Eucalyptus robusta (12 mm). Essential oils from the leaves of Eucalyptus alba, Eucalyptus citriodora, Eucalyptus deglupta, Eucalyptus globulus, Eucalyptus saligna, Eucalyptus robusta, Aframomum stipulatum, Cymbopogon citratus, Ocimum americanum and that of the seeds of Monodora myristica showed also a good antibacterial activity (10–18 mm). Eucalyptus propinqua, Eucalyptus urophylla and Ocimum gratissimum essential oils were the less active samples against the selected bacteria. No correlation between the amount of major constituents such as 1,8-cineol, α-pinene, p-cymene, cryptone or thymol and the antibacterial activity was observed. [Copyright &y& Elsevier]

The article reports on the potential of a nutritional supplement combining red yeast rice and olive fruit extract on people wit metabolic syndrome's (MetS) lipid profile and on oxidative stress.

The ethanolic, dichloromethane and lyophilized aqueous extracts of Cassia occidentalisroot bark, Morinda morindoidesleaves and whole plants of Phyllanthus niruriwere evaluated for their antimalarial activity in vivo, in 4-day, suppressive assays against Plasmodium bergheiANKA in mice. No toxic effect or mortality was observed in mice treated, orally, with any of the extracts as a single dose, of 500 mg/kg body weight, or as the same dose given twice weekly for 4 weeks (to give a total dose of 4 g/kg). No significant lesions were observed, by eye or during histopathological examinations, in the hearts, lungs, spleens, kidneys, livers, large intestines or brains of any mouse. :At doses of 200 mg/kg, all the ethanolic and dichloromethane extracts produced significant chemosuppressions of parasitaemia (of >60% for C. occidentalisroot bark and Ph. niruriwhole plant, and of 30% for M. morindoidesleaves) when administered orally. The most active ethanolic extract, that of Ph. niruri, reduced parasitaemia by 73%. The dichloromethane extracts of M. morindoidesand Ph. niruriproduced similar reductions (74% and 72% chemosuppression, respectively), whereas that of C. occidentaliswas slightly less active (60% chemosuppression). Each lyophilized aqueous extract was less active than the corresponding ethanolic extract. [ABSTRACT FROM AUTHOR]

Background: Olive leaves are a rich source of polyphenols, predominantly secoiridoids, flavonoids, and simple phenols, which exhibit various biological properties. Extracts prepared from olive leaves are associated with hypoglycemic, hypotensive, diuretic, and antiseptic properties. Upon ingestion, a substantial fraction of these polyphenols reaches the colon where they undergo extensive metabolism by the gut microbiota. Host characteristics, like age, can influence the composition of the gut microbiome, potentially affecting the biotransformation of these compounds. Therefore, it can be hypothesised that differences in the gut microbiome between young and elderly individuals may impact the biotransformation rate and the type and amount of metabolites formed., Methods: An in vitro biotransformation model was used to mimic the conditions in the stomach, small intestine and colon of two age groups of healthy participants (20-30 years old, ≥65 years old), using oleuropein as a single compound and an olive leaf extract as test compounds. The bacterial composition and metabolite content were investigated., Results: The study revealed that, while the same metabolites were formed in both age groups, in the young age group, less metabolite formation was observed, likely due to a reduced viable cell count. Most biotransformation reactions took place within the first 24 h of colon incubation, and mainly, deglycosylation, hydrolysis, flavonoid ring cleavage, and demethylation reactions were observed. A bacterial composition analysis showed a steep drop in α-diversity after 24 h of colon incubation, likely due to favourable experimental conditions for certain bacterial species., Conclusions: Both age groups produced the same metabolites, suggesting that the potential for polyphenols to exert their health-promoting benefits persists in healthy older individuals.

Background: Diabetes ranks among the most common chronic conditions in childhood and adolescence. It is unique among chronic conditions, in that clinical outcomes are intimately tied to how the child or adolescent living with diabetes and their parents or carers react to and implement good clinical practice guidance. It is widely recognized that the individual's perspective about the impact of trying to manage the disease together with the burden of self-management should be addressed to achieve optimal health outcomes. Standardized, rigorous assessment of behavioural and mental health outcomes is crucial to aid understanding of person-reported outcomes alongside, and in interaction with, physical health outcomes. Whilst tempting to conceptualize person-reported outcomes as a focus on perceived quality of life, the reality is that health-related quality of life is multi-dimensional and covers indicators of physical or functional health status, psychological well-being and social well- being., Methods: In this context, this Consensus Statement has been developed by a collection of experts in diabetes to summarize the central themes and lessons derived in the assessment and use of person-reported outcome measures in relation to children and adolescents and their parents/carers, helping to provide a platform for future standardization of these measures for research studies and routine clinical use., Results: This consensus statement provides an exploration of person-reported outcomes and how to routinely assess and incorporate into clincial research., (© 2024 Diabetes UK.)

Glutathione (GSH), a tripeptide that consists of cysteine, glutamate and glycine, is present in all mammalian tissues in the millimolar range. Besides having numerous cellular functions, GSH is an important antioxidant and is considered a valuable biomarker in evaluating oxidative stress. This paper provides a sensitive analytical method using HPLC-ECD to quantify GSH in erythrocytes, validated using the ICH guidelines for Bioanalytical Method Validation. The sample preparation was optimised using centrifugal filtration and a hypotonic phosphate buffer for extracting GSH from erythrocytes. HPLC-ECD parameters were adjusted to allow a fast, reversed phase, isocratic separation in 10 min. The detector response was linear between 0.3 and 9.5 μg/mL with a satisfactory regression coefficient and a LOQ of 0.11 μg/mL. Intra- and inter-day repeatability ranged between 1.10% and 8.57% with recoveries ranging from 94.3% to 106.0%. Dilution integrity, benchtop, freeze-thaw and long-term stability were investigated. Samples were stable for up to 6 months at -80°C. This method has a good linear response and is repeatable, precise and accurate. It minimises GSH auto-oxidation using a centrifugal filter during sample preparation, instead of acidification. Therefore, this analytical method is suitable for quantifying GSH in erythrocytes as a marker of oxidative stress., (© 2024 The Author(s). Biomedical Chromatography published by John Wiley & Sons Ltd.)

Mycobacterium tuberculosis complex (MTBC) whole genome sequencing (WGS) turnaround time and WGS success rates are highly influenced by DNA extraction protocols even from cultures. Efficient mycobacterial lysis is crucial for obtaining sufficient DNA from cultures to facilitate reliable genomic drug susceptibility prediction and accurate genotyping with WGS. We compared four DNA extraction protocols from BD BACTEC™ Mycobacterial Growth Indicator Tubes (MGIT) for WGS with a focus on the lysis step: protocol A) column-based protocol without mechanical lysis; protocol B) an adapted protocol including a bead beating step; protocol C) DNA extraction from primary received cultures using bead beating: and protocol D) DNA extraction from pre MGIT-positive (enriched) cultures. Protocol B increased DNA yield approximately 60-fold, and significantly improved the sequencing success rate. The increased yield also allowed DNA extraction from primary cultures with high success rates (protocol C). Additionally, by using pre-positive enriched MGIT cultures, we demonstrated that bead beating opens the possibility of reliable WGS up to five days before a MGIT tube would be flagged positive (protocol D). The most optimal bead beating-based DNA extraction was also evaluated for Nanopore sequencing. Shortening bead beating duration to 15 s resulted in longer read lengths (N50 from 1.4 kb to 2.6 kb) while still providing efficient lysis. Furthermore, AmpureXP bead beating-based DNA capture / purification proved to be as efficient as Qiagen column-based DNA extraction, further simplifying and shortening the DNA extraction protocol. Adding a mechanical lysis step to our routine MTBC DNA extraction protocol has allowed us to reduce the turnaround time while maintaining DNA quality sequencing success rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kristin Kremer, Noud Hermans, Richard Anthony reports financial support was provided by Netherlands National Postcode Lottery. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Tert-butylphenol (TBP) derivatives, antioxidants in adhesives and diabetes devices, may provoke allergic contact dermatitis (ACD)., Objectives: The objective of this study is to report sensitization to TBP derivatives in medical devices and to highlight that tert-butylhydroquinone (BHQ) and tert-butylcatechol (TBC) are potential screeners in this regard., Methods: Fifteen patients with ACD from adhesives and diabetes devices were patch tested to different TBPs: BHQ 1% pet., TBC 0.25% pet., BHA 2% pet., BHT 2% pet., 4-tert-butylphenol (TBP) 1% pet. and 2,4-di-tert-butylphenol (di TBP) 1% pet. The culprit devices (medical adhesives, sanitary pads, diabetes devices) and TBP patch preparations were analysed using gas chromatography-mass spectrometry (GC-MS)., Results: BHQ (9/13), TBC (7/13), and to a lesser extent BHT (3/15), BHA (2/15) and TBP (2/13) gave positive reactions. Seven patients had developed ACD from adhesives and diabetes devices, respectively, and one patient from sanitary pads. GC-MS analyses of the medical devices and patch test materials confirmed the presence of the patch-test positive TBPs, or chemically related derivatives, or, interestingly, tert-butylbenzoquinones (BBQ) were found, that is, spontaneously formed, highly reactive TBP metabolites, likely (pseudo-) cross reacting with the patch tested TBPs., Conclusion: TBPs might be overlooked sensitizers in medical devices, and BHQ and TBC are potential screeners in this regard., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Several Flaviviridae constitute an emerging threat to global health because of their continuing spread and the expansion of vector habitats, largely driven by climate change and intensified global travel. Infections can result in severe neurological or visceral pathologies. The relationship between oxidative stress (OS), an imbalance between generated reactive oxygen species and the antioxidant defences of the host, and flavivirus infection has been repeatedly demonstrated in in vitro and animal studies, but measuring biomarkers of oxidative stress in vivo could prove useful in clinical patient management. We summarise the knowledge and prospects of measuring peripheral OS biomarker levels for clinical case management and correlation with disease severity in six important human flavivirus infections (dengue virus (DENV), Japanese encephalitis virus, West Nile virus (WNV), tick-borne encephalitis virus (TBEV), yellow fever virus and zika virus). We searched the Medline and Web of Science databases for 'Oxidative Stress' AND 'Biomarkers' AND 'Flavivirus', combined with 'clinical', 'in vivo/in vivo', 'patient' and/or 'disease' and included 43 peer-reviewed publications. Correlation between OS and infection has been studied in all six Flaviviridae, but most clinically relevant data are available for DENV, TBEV and WNV. Plasma protein carbonyls, glutathione peroxidase activity and nitrogen monoxide are promising prognostic markers, but their measurement would benefit from methodological harmonisation. Future studies should investigate a broad range of OS biomarkers as predictors of clinically relevant outcomes. We advocate the validation and use of universal or disease-specific oxidative stress indexes that incorporate the most significant outcomes into one, easy-to-use clinical determinant., (© 2024 The Author(s). Reviews in Medical Virology published by John Wiley & Sons Ltd.)

Introduction: The pathogenesis of Attention-Deficit Hyperactivity Disorder (ADHD) is thought to be multifactorial, with a potential role for the bidirectional communication between the gut microbiome and brain development and function. Since the "golden-standard" medication therapy with methylphenidate (MPH) is linked to multiple adverse effects, there is a need for alternative treatment options such as dietary polyphenols. These secondary plant metabolites exert antioxidant and anti-inflammatory effects, but much less is known about their impact on the gut microbiota. Since polyphenols are believed to modulate gut microbial composition, interventions might be advantageous in ADHD therapy. Therefore, intervention studies with polyphenols in ADHD therapy investigating the gut microbial composition are highly relevant., Methods: Besides the primary research questions addressed previously, this study explored a potential prebiotic effect of the polyphenol-rich French Maritime Pine Bark Extract (PBE) compared to MPH and a placebo in pediatric ADHD patients by studying their impact on the gut microbiota via amplicon sequencing of the full length 16S rRNA gene ribosomal subunit (V1-V9)., Results: One interesting finding was the high relative abundance of Bifidobacteria among all patients in our study cohort. Moreover, our study has identified that treatment (placebo, MPH and PBE) explains 3.94% of the variation in distribution of microbial taxa (adjusted p -value of 0.011)., Discussion: Our small sample size (placebo: n  = 10; PBE: n  = 13 and MPH: n  = 14) did not allow to observe clear prebiotic effects in the patients treated with PBE. Notwithstanding this limitation, subtle changes were noticeable and some limited compositional changes could be observed., Clinical Trial Registration: doi: 10.1186/S13063-017-1879-6., Competing Interests: SL is an academic board member of the International Scientific Association on Probiotics and Prebiotics ISAPP (www.isappscience.org) she is a co-founder of YUN and has received industrial research funding from DSM, Lesaffre, YUN, Puratos, Pathosense and BioOrg/Metatecta. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Weyns, Ahannach, Van Rillaer, De Bruyne, Lebeer and Hermans.)

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data., (© 2024 Diabetes UK.)

Ferroptosis is a type of regulated necrosis that is associated with iron-dependent accumulation of lipid hydroperoxides. Given that iron deposition and lipid peroxidation initiate ferroptosis in atherosclerosis and contribute to further plaque development, we hypothesized that inhibition of ferroptosis could be of value in the treatment of atherosclerosis. Glutathione peroxidase 4 (GPX4) is the only enzyme known capable of reducing lipid hydroperoxides. Previous studies have demonstrated that inactivation of GPX4 results in ferroptosis, while overexpression of GPX4 confers resistance to ferroptosis. In the present study, we examined the impact of GPX4 overexpression on the development of atherosclerotic plaques. GPX4-overexpressing mice (GPX4Tg/+) were crossbred with ApoE-/- mice and fed a western-type diet for 16 weeks. Atherosclerotic plaques of GPX4Tg/+ ApoE-/- mice showed increased GPX4 expression and a reduced amount of lipid hydroperoxides. However, plaque size and composition were not different as compared to control animals. Similarly, GPX4-overexpressing vascular smooth muscle cells and bone marrow-derived macrophages were not protected against lipid peroxidation and cell death triggered by the ferroptosis inducers erastin and 1S,3R-RSL3. We concluded that GPX4 overexpression reduces lipid peroxidation in plaques of ApoE-/- mice, yet GPX4 overexpression is not sufficiently powerful to change plaque size or composition.

The impact of α-tocopherol on atherosclerosis is unclear and controversial. While some studies suggest potential benefits, such as antioxidant properties that may reduce oxidative stress, other studies indicate no significant preventive effects. The intricate interplay of various factors, including dosage, individual differences, and study methodologies, contributes to the ongoing uncertainty surrounding α-tocopherol's role in atherosclerosis. Further research is needed to clarify its impact and establish clearer guidelines. Therefore, we aimed to evaluate the impact of α-tocopherol on atherogenesis in ApoE-/- fibrillin (Fbn)1C1039G/+ mice, which is a unique mouse model of advanced atherosclerosis with typical features, such as large necrotic cores, high levels of inflammation, and intraplaque neovascularization, that resemble the unstable phenotype of human plaques. ApoE-/- Fbn1C1039G+/- mice were fed a western-type diet (WD) supplemented with a high dose of α-tocopherol (500 mg/kg diet), while control mice were fed a WD containing a low dose of α-tocopherol (50 mg/kg diet). The high dose of α-tocopherol reduced plaque thickness and necrotic core area in the right common carotid artery (RCCA) after 24 weeks WD. Moreover, α-tocopherol decreased plaque formation and intraplaque neovascularization in the RCCA. In addition to its antiatherogenic effect, chronic supplementation of α-tocopherol improved cardiac function in ApoE-/- Fbn1C1039G/+ mice. However, chronic supplementation of α-tocopherol did not decrease lipid peroxidation. On the contrary, α-tocopherol acted as a prooxidant by increasing plasma levels of oxidized LDL and plaque malondialdehyde, an end product of lipid peroxidation. Our data indicate that α-tocopherol inhibits atherogenesis and improves cardiac function independent of its antioxidant properties.

Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound 26 /HIT 8. We previously identified this molecule as a 'hit' during a high-throughput screening campaign for autophagy inducers. A variety of synthetic strategies were utilized to modify the 1,3-diarylpyrazole core at its 1-, 3-, and 4-position. Compounds were assessed in vitro to identify their cytotoxicity properties. Of note, several compounds in the series displayed relevant cytotoxicity, which warrants scrutiny while interpreting biological activities that have been reported for structurally related molecules. In addition, antiparasitic activities were recorded against a range of human-infective protozoa, including Trypanosoma cruzi , T. brucei rhodesiense , and Leishmania infantum . The most interesting compounds displayed low micromolar whole-cell potencies against individual or several parasitic species, while lacking cytotoxicity against human cells.

Global aflatoxin contamination of agricultural commodities is of the most concern in food safety and quality. This study investigated the hepatoprotective effect of 80% methanolic leaf extract of Annona senegalensis against aflatoxin B1 (AFB1)-induced toxicity in rats. A. senegalensis has shown to inhibit genotoxicity of aflatoxin B1 in vitro. The rats were divided into six groups including untreated control, aflatoxin B1 only (negative control); curcumin (positive control; 10 mg/kg); and three groups receiving different doses (100 mg/kg, 200 mg/kg, and 300 mg/kg) of A. senegalensis extract. The rats received treatment (with the exception of untreated group) for 7 days prior to intoxication with aflatoxin B1. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were measured. Hepatic tissues were analysed for histological alterations. Administration of A. senegalensis extract demonstrated hepatoprotective effects against aflatoxin B1-induced toxicity in vivo by significantly reducing the level of serum aspartate aminotransferase and alanine aminotransferase and regenerating the hepatocytes. No significant changes were observed in the levels of alkaline phosphatase, lactate dehydrogenase, and creatinine for the AFB1 intoxicated group, curcumin+AFB1 and Annona senegalensis leaf extract (ASLE)+AFB1 (100 mg/kg, 200 mg/kg, and 300 mg/kg body weight [b.w.]) treated groups. Annona senegalensis is a good candidate for hepatoprotective agents and thus its use in traditional medicine may at least in part be justified.Contribution: The plant extract investigated in this study can be used in animal health to protect the organism from toxicity caused by mycotoxins.

Catechins have proven to have several health benefits, yet a huge interindividual variability occurs. The metabolic potency of the colonic microbiota towards catechin is a key determinant of this variability. Microbiota from two donors - previously characterized as a fast and a slow converter- were incubated with (+)-catechin in vitro. The robustness of in vitro metabolic profiles was verified by well-fitted human trials. The colon region-dependent and donor-dependent patterns were reflected in both metabolic features and colonic microbiota composition. Upstream and downstream metabolites were mainly detected in the proximal and distal colons, respectively, and were considered important explanatory variables for microbiota clustering in the corresponding colon regions. Higher abundances of two catechin-metabolizing bacteria, Eggerthella and Flavonifractor were found in the distal colon compared to the proximal colon and in slow converter than fast converter. Additionally, these two bacteria were enriched in treatment samples compared to sham treatment samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

(1) Background: Filipendula ulmaria (L.) Maxim. (Rosaceae) (meadowsweet) is widely used in phytotherapy against inflammatory diseases. However, its active constituents are not exactly known. Moreover, it contains many constituents, such as flavonoid glycosides, which are not absorbed, but metabolized in the colon by gut microbiota, producing potentially active metabolites that can be absorbed. The aim of this study was to characterize the active constituents or metabolites. (2) Methods: A F. ulmaria extract was processed in an in vitro gastrointestinal biotransformation model, and the metabolites were characterized using UHPLC-ESI-QTOF-MS analysis. In vitro anti-inflammatory activity was evaluated by testing the inhibition of NF-κB activation, COX-1 and COX-2 enzyme inhibition. (3) Results: The simulation of gastrointestinal biotransformation showed a decrease in the relative abundance of glycosylated flavonoids such as rutin, spiraeoside and isoquercitrin in the colon compartment, and an increase in aglycons such as quercetin, apigenin, naringenin and kaempferol. The genuine as well as the metabolized extract showed a better inhibition of the COX-1 enzyme as compared to COX-2. A mix of aglycons present after biotransformation showed a significant inhibition of COX-1. (4) Conclusions: The anti-inflammatory activity of F. ulmaria may be explained by an additive or synergistic effect of genuine constituents and metabolites.

Saponin-rich sea cucumber extracts have shown antidiabetic effects in a few reports. Although the triterpene glycosides of sea cucumbers are commonly isolated from their Cuvierian tubules, these are absent in Holothuria atra Jaeger. Therefore, this study intended to investigate the saponin profile in the body wall of H. atra , as well as to assess the α-glucosidase inhibitory activity of the H. atra extracts. The chemical profiling of sea cucumber extracts was conducted by UPLC-HRMS analysis. This resulted in the tentative identification of 11 compounds, 7 of which have not been reported in the H. Atra body wall before. Additionally, two triterpene glycosides were purified and their structures were elucidated based on HRMS and NMR data: desholothurin B (1), and a novel epimer, 12-epi-desholothurin B (2). Moreover, the fatty acid profile of the H. atra body wall was investigated by GC-MS. It was found that the Me90 fraction of the H. atra body wall showed the strongest α-glucosidase inhibitory activity (IC 50 value 0.158 ± 0.002 mg/mL), thus making it more potent than acarbose (IC 50 value 2.340 ± 0.044 mg/mL).

West Nile virus (WNV) can cause asymptomatic infection in humans, result in self-limiting febrile illness, or lead to severe West Nile Neuroinvasive disease (WNND). We conducted a pilot study to compare selected biomarkers of oxidative stress in sera of viremic West Nile virus patients and asymptomatic infected blood donors to investigate their potential as predictors of disease severity. We found that total oxidant status was elevated in WNND and in uncomplicated WNV infections (median 9.05 (IQR 8.37 to 9.74) and 7.14 (7.03 to 7.25) µmol H 2 O 2 equiv./L, respectively) compared to asymptomatic infections (0.11 (0.07 to 0.19) µmol H 2 O 2 equiv./L) ( p = 0.048). MDA levels showed a similar trend to TOS, but differences were not significant at α = 0.05. Total antioxidant status did not differ significantly between different disease severity groups. Oxidative stress appears to be associated with more severe disease in WNV-infected patients. Our preliminary findings warrant prospective studies to investigate the correlation of oxidative stress with clinical outcomes and severity of WNV infection.

To detect cognitive change after brain damage, it is important to know the level of premorbid intellectual functioning. A popular instrument in this context is the "Nederlandse Leestest voor Volwassenen" (NLV; Schmand et al., 1992). In this test, 50 words with irregular pronunciation must be read out loud. The score on this test used to be considered as a good estimate of someone's premorbid IQ, due to high correlations with the Verbal and Full-Scale IQ estimates of the WAIS (Verbal IQ: r = .85, Full Scale IQ: r = .74; Schmand et al., 1992). Despite some updates of the normative data (e.g., Bouma et al., 2012), the validity of the test has not been re-evaluated since. The aim of the current study was to evaluate whether the NLV still correlates sufficiently with the WAIS-IV to warrant its proper use as a psychodiagnostic tool. In Study 1, 30 participants (age range: 20-29 year) were tested, and in Study 2, 51 participants (age range: 45-65 year). We checked whether the NLV-generated IQ-score estimates correlated with the different IQ indices of the WAIS-IV. In the younger group, no correlations were found between the NLV-generated IQ-score estimate and any of the WAIS-IV indices nor the Full-Scale IQ. In the older group, the NLV-generated IQ-score estimate correlated with Full scale IQ and the indices of Verbal Comprehension, Working Memory and Processing Speed. These correlations were all <.46 which is far below the typically hold standard in test development of >.70. Based on these findings we conclude the NLV in its current form is not appropriate anymore to estimate premorbid IQ in both young and older adults., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Background: Type 2 diabetes mellitus (T2DM) is associated with a high risk of vascular complications. Interestingly, cocoa flavanols (CF) can exert beneficial vascular effects in non-diabetic subjects. However, these effects have only been scarcely studied in T2DM. Therefore, we performed a study to assess the effects on vascular reactivity of a single dose of CF (790 mg) in T2DM and whether certain antihypertensive drugs may modulate these effects., Methods: 24 non-diabetic and 11 T2DM subjects were studied in a cross-over design. Fasting blood samples, blood pressure (BP), and arterial vasoreactivity (flow-mediated dilation) were assessed before and 70 min after capsule ingestion. Muscle microvascular reactivity was only assessed after capsule ingestion. Age, waist-to-hip ratio, BP at baseline, and the use of antihypertensive drugs were regarded as covariates in a mixed models analysis., Results: CF ingestion did not affect any parameter. However, independent of the type of capsules ingested, a decrease in diastolic BP by 3 mmHg (95% CI: -4.0; -2.0) and an increase in the change in brachial artery diameter (pre vs. post occlusion) by 0.06 mm (95% CI: 0.01; 0.12) were detected in the non-diabetic group, while they remained unchanged in the T2DM group., Conclusion: No beneficial effects of CF were detected on vascular reactivity parameters in T2DM and non-diabetic participants.

Riboflavin-producing lactic acid bacteria represent a promising and cost-effective strategy for food biofortification, but production levels are typically insufficient to support daily human requirements. In this study, we describe the novel human isolate Limosilactobacillus reuteri AMBV339 as a strong food biofortification candidate. This strain shows a high natural riboflavin (vitamin B2) overproduction of 18.36 μg/ml, biomass production up to 6 × 10 10 colony-forming units/ml (in the typical range of model lactobacilli), and pH-lowering capacities to a pH as low as 4.03 in common plant-based (coconut, soy, and oat) and cow milk beverages when cultured up to 72 h at 37°C. These properties were especially pronounced in coconut beverage and butter milk fermentations, and were sustained in co-culture with the model starter Streptococcus thermophilus . Furthermore, L. reuteri AMBV339 grown in laboratory media or in a coconut beverage survived in gastric juice and in a simulated gastrointestinal dialysis model with colon phase (GIDM-colon system) inoculated with fecal material from a healthy volunteer. Passive transport of L. reuteri AMBV339-produced riboflavin occurred in the small intestinal and colon stage of the GIDM system, and active transport via intestinal epithelial Caco-2 monolayers was also demonstrated. L. reuteri AMBV339 did not cause fecal microbiome perturbations in the GIDM-colon system and inhibited enteric bacterial pathogens in vitro . Taken together, our data suggests that L. reuteri AMBV339 represents a promising candidate to provide riboflavin fortification of plant-based and dairy foods, and has a high application potential in the human gastrointestinal tract., Competing Interests: A patent application EP20210606.8 (owned by the University of Antwerp and with SA, IS, SW, and SL as inventors) has been submitted based on the results described in this manuscript. SL has received (research) funding from several companies, but they were not involved in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Spacova, Ahannach, Breynaert, Erreygers, Wittouck, Bron, Van Beeck, Eilers, Alloul, Blansaer, Vlaeminck, Hermans and Lebeer.)