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Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article, we reported the synthesis of a series of new hybrid molecules through merging the structural features of chalcones and pyridothienopyrimidinones. Our results indicated that the synthesis of chalcone-thienopyrimidine derivatives from the corresponding thienopyrimidine and chalcones proceeded in a relatively short reaction time with good yields and high purity. Most of these novel compounds exhibited moderate to robust cytotoxicity against HepG2 and MCF-7 cancer cells similar to that of 5-fluorouracil (5-FU). The results indicated that IC 50 of the two compounds ( 3b and 3g ) showed more potent anticancer activities against HepG2 and MCF-7 than 5-FU. An MTT assay and flow cytometry showed that only 3b and 3g had anticancer activity and antiproliferative activities at the G1 phase against MCF-7 cells, while six compounds ( 3a - e and 3g ) had cytotoxicity and cell cycle arrest at different phases against HepG2 cells. Their cytotoxicity was achieved through downregulation of Bcl-2 and upregulation of Bax, caspase-3, and caspase-9. Although all tested compounds increased oxidative stress via increment of MDA levels and decrement of glutathione reductase (GR) activities compared to control, the 3a , 3b , and 3g in HepG2 and 3b and 3g in MCF-7 achieved the target results. Moreover, there was a positive correlation between cytotoxic efficacy of the compound and apoptosis in both HepG2 ( R 2 = 0.531; P = 0.001) and MCF-7 ( R 2 = 0.219; P = 0.349) cell lines. The results of molecular docking analysis of 3a-g into the binding groove of Bcl-2 revealed relatively moderate binding free energies compared to the selective Bcl-2 inhibitor, DRO. Like venetoclax, compounds 3a-g showed 2 violations from Lipinski's rule. However, the results of the ADME study also revealed higher drug-likeness scores for compounds 3a-g than for venetoclax. In conclusion, the tested newly synthesized chalcone-pyridothienopyrimidinone derivatives showed promising antiproliferative and apoptotic effects. Mechanistically, the compounds increased ROS production with concomitant cell cycle arrest and apoptosis. Therefore, regulation of the cell cycle and apoptosis are possible targets for anticancer therapy. The tested compounds could be potent anticancer agents to be tested in future clinical trials after extensive pharmacodynamic, pharmacokinetic, and toxicity profile investigations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Ghada M. Safwat et al.)

The biological and therapeutic properties of seaweeds have already been well known. Several studies showed that among the various natural marine sources of antioxidants, seaweeds have become a potential source of antioxidants because of their bioactive compounds. Most of the metabolic diseases are caused by oxidative stress. It is very well known that antioxidants have a pivotal role in the treatment of those diseases. Recent researches have revealed the potential activity of seaweeds as complementary medicine, which have therapeutic properties for health and disease management. Among the seaweeds, brown seaweeds (Phaeophyta) and their derived bioactive substances showed excellent antioxidant properties than other seaweeds. This review focuses on brown seaweeds and their derived major bioactive compounds such as sulfated polysaccharide, polyphenol, carotenoid, and sterol antioxidant effects and molecular mechanisms in the case of the oxidative stress-originated disease. Antioxidants have a potential role in the modification of stress-induced signaling pathways along with the activation of the oxidative defensive pathways. This review would help to provide the basis for further studies to researchers on the potential antioxidant role in the field of medical health care and future drug development., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Rahima Begum et al.)

Neurodegenerative disorders (NDs) are heterogeneous groups of ailments typically characterized by progressive damage of the nervous system. Several drugs are used to treat NDs but they have only symptomatic benefits with various side effects. Numerous researches have been performed to prove the advantages of phytochemicals for the treatment of NDs. Furthermore, phytochemicals such as polyphenols might play a pivotal role in rescue from neurodegeneration due to their various effects as anti-inflammatory, antioxidative, and antiamyloidogenic agents by controlling apoptotic factors, neurotrophic factors (NTFs), free radical scavenging system, and mitochondrial stress. On the other hand, neurotrophins (NTs) including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT4/5, and NT3 might have a crucial neuroprotective role, and their diminution triggers the development of the NDs. Polyphenols can interfere directly with intracellular signaling molecules to alter brain activity. Several natural products also improve the biosynthesis of endogenous genes encoding antiapoptotic Bcl-2 as well as NTFs such as glial cell and brain-derived NTFs. Various epidemiological studies have demonstrated that the initiation of these genes could play an essential role in the neuroprotective function of dietary compounds. Hence, targeting NTs might represent a promising approach for the management of NDs. In this review, we focus on the natural product-mediated neurotrophic signal-modulating cascades, which are involved in the neuroprotective effects., Competing Interests: The authors proclaim no competing interests., (Copyright © 2021 Md Sahab Uddin et al.)

The brain is a sexually dimorphic organ that implies different functions and structures depending on sex. Current pharmacological approaches against different neurological diseases act distinctly in male and female brains. In all neurodegenerative diseases, including Alzheimer's disease (AD), sex-related outcomes regarding pathogenesis, prevalence, and response to treatments indicate that sex differences are important for precise diagnosis and therapeutic strategy. Pathogenesis of AD includes vascular dementia, and in most cases, this is accompanied by metabolic complications with similar features as those assembled in diabetes. This review discusses how AD-associated dementia and diabetes affect cognition in relation to sex difference, as both diseases share similar pathological mechanisms. We highlight potential protective strategies to mitigate amyloid-beta (A β ) pathogenesis, emphasizing how these drugs act in the male and female brains., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Ghulam Md Ashraf et al.)

Spinal cord injury (SCI) is a damage or trauma to the spinal cord resulting in a total or partial loss of motor and sensory function. SCI is characterized by a disequilibrium between the production of reactive oxygen species and the levels of antioxidant defences, causing oxidative stress and neuroinflammation. This review is aimed at highlighting the hormetic effects of some compounds from foods, beverages, and food dressing that are able to reduce oxidative stress in patients with SCI. Although curcumin, ginseng, and green tea have been proposed for SCI management, low levels of antioxidant vitamins have been reported in individuals with SCI. Mediterranean diet includes food rich in vitamins and antioxidants. Moreover, food dressing, including spices, herbs, and extra virgin olive oil (EVOO), contains multiple components with hormetic effects. The latter involves the activation of the nuclear factor erythroid-derived 2, consequently increasing the antioxidant enzymes and decreasing inflammation. Furthermore, EVOO improves the bioavailability of carotenoids and could be a delivery system for bioactive compounds. In conclusion, Mediterranean dressing in addition to plant foods can have an important effect on redox balance in individuals with SCI., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Anna Lucia Fedullo et al.)

Background: Urinary tract infection (UTI) is common in individuals with spinal cord injury (SCI) and neurogenic lower urinary tract dysfunction (NLUTD) and in veterans with SCI who use antibiotics improperly for asymptomatic bacteriuria. Cranberry (CB) has been suggested for UTI prevention., Methods: We performed a systematic search up to May 2020 in the following databases: AccessMedicine, BioMed Central, CINAHL, Cochrane Library, ProQuest, and PubMed. Quality assessment was performed using a specifically designed quality score. Risk ratio was calculated with both random effect model analysis (DerSimonian-Laird method) and quality effect model analysis (Doi Thalib method)., Results: Six studies on bacteriuria and SCI were reviewed. From the four studies available for meta-analysis, two of which with individuals taking both CB and control, 477 data from 415 participants were analysed (241 CB and 236 control). No significant differences were detected with meta-analysis. However, bias, limitations, and incompleteness were observed in the reviewed studies., Conclusion: Although further studies are needed, we suggest an accurate monitoring of diet and fluid intake, the evaluation of risk for potential food or nutraceutical interactions with drugs, and the inclusion of inflammatory markers among the outcomes in addition to UTI., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Anna Raguzzini et al.)

Background: Both antioxidant and prooxidant activities have been previously reported for cerium oxide (CeO 2 ). The aim of this study was to investigate the effects of CeO 2 at different doses on changes in kidney tissues and markers in neonatal mice., Methods: We randomly divided 30 pregnant NMRI mice into five groups ( n = 6 per group)-a control group and four groups treated with intraperitoneal (i.p.) administration of different doses of CeO 2 (10, 25, 80, or 250 mg/kg body weight (bw)) on gestation days (GD) 7 and GD14. At the end of the treatment period, we analyzed the kidney tissues and serum samples. The levels of two serum redox markers, malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP), were determined. Data were analyzed using one-way ANOVA and Tukey's test, and a P value of <0.05 was considered significant., Results: The mean total volumes of the renal corpuscle, glomeruli, and Bowman's capsule membranes significantly increased, and there was a significant decrease in the mean total volume of Bowman's space in the high-dose CeO 2 group compared to that in the control group. No statistically significant differences existed in the serum levels of MDA and FRAP in the treated and control groups., Conclusion: Our results suggest that high doses of CeO 2 impair fetal renal development in pregnant mice, which results in kidney damage. Therefore, CeO 2 administration during pregnancy could have dose-dependent adverse effects on the developing kidneys in neonates., Competing Interests: There is no conflict of interest related to this research., (Copyright © 2020 Afsaneh Nemati et al.)

Competing Interests: The editors declare that they have no conflicts of interest regarding the publication of this special issue.

The standard treatment for cancer is generally based on using cytotoxic drugs, radiotherapy, chemotherapy, and surgery. However, the use of traditional treatments has received attention in recent years. The aim of the present work was to provide an overview of medicinal plants effective on colon cancer with special emphasis on bioactive components and underlying mechanisms of action. Various literature databases, including Web of Science, PubMed, and Scopus, were used and English language articles were considered. Based on literature search, 172 experimental studies and 71 clinical cases on 190 plants were included. The results indicate that grape, soybean, green tea, garlic, olive, and pomegranate are the most effective plants against colon cancer. In these studies, fruits, seeds, leaves, and plant roots were used for in vitro and in vivo models. Various anticolon cancer mechanisms of these medicinal plants include induction of superoxide dismutase, reduction of DNA oxidation, induction of apoptosis by inducing a cell cycle arrest in S phase, reducing the expression of PI3K, P-Akt protein, and MMP as well; reduction of antiapoptotic Bcl-2 and Bcl-xL proteins, and decrease of proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin B1 and cyclin E. Plant compounds also increase both the expression of the cell cycle inhibitors p53, p21, and p27, and the BAD, Bax, caspase 3, caspase 7, caspase 8, and caspase 9 proteins levels. In fact, purification of herbal compounds and demonstration of their efficacy in appropriate in vivo models, as well as clinical studies, may lead to alternative and effective ways of controlling and treating colon cancer., Competing Interests: There is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Paola Aiello et al.)

Berberis vulgaris is a well-known herb in Iran that is widely used as a medicinal plant and a food additive. The aim of this study was to investigate the anti-inflammatory and immunomodulatory effects of Barberry and its main compounds. This narrative review was conducted by searching keywords such as B . vulgaris , Barberry, immunomodulatory, anti-inflammatory, medicinal herbs, plants, and extract, separately or combined in various databases, such as Web of Sciences, PubMed, and Scopus. According to the inclusion and exclusion criteria, just English language articles, which reported effective whole plants or herbal compounds, were included. 21 articles were reviewed in this study. In the in vivo models (mice, rats, and human cells) and in the in vitro models (some organ cells such as the spleen, kidney, blood, and brain), B . vulgaris and its main components showed anti-inflammatory effects in both models. The main mechanisms were the shift of cell immune response to Th2, T reg induction, inhibition of inflammatory cytokines (IL-1, TNF, and IFN- γ ), and stimulation of IL-4 and IL-10. The induction of apoptosis in APCs and other effector cells was another important mechanism., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2019 Rasool Nasiri Kalmarzi et al.)

Haematological indexes of both inflammation and platelet activation have been suggested as predictive markers of cardiovascular disease (CVD), which has high prevalence in Paralympic athletes (PA). Different mechanisms could play a role in increasing CVD risk in PA with spinal cord injury (PA-SCI), lower limb amputation (PA-LLA), or upper limb impairment (PA-ULI). We compared, in 4 groups of PA competing in power, intermittent (mixed metabolism), and endurance sports, Framingham Risk Score (FRS), metabolic syndrome criteria (MetS-C), inflammation (INFLA) Score, 5 haematological indexes of platelet activation (mean platelet volume (MPV), platelet distribution width (PDW), and the ratios between MPV and platelet (MPVPR), between MPV and lymphocyte (MPVLR), and between PDW and lymphocyte (PDWLR)) and the endogenous antioxidants uric acid (UA) and bilirubin (BR). A retrospective chart review of PA from preparticipation examinations' records (London 2012 and Sochi 2014 Paralympics) was performed. We included 25 PA-SCI (13 with high and 12 with low lesion, PA-SCI-H and PA-SCI-L), 15 PA-LLA, and 10 PA-ULI. FRS and INFLA Score did not differ among groups, but PA-SCI-H had lower HDL, compared to PA-SCI-L and PA-ULI. PA-LLA had more MetS diagnostic criteria with significant higher glucose levels than other groups. PA-SCI-H had significantly lower lymphocytes' count compared to PA-LLA and higher MPV, PDW, MPVPR, MPVLR, and PDWLR. SCI-H had lower BR, haemoglobin, haematocrit, proteins, and creatinine. No interaction was found between the 3 kinds of sitting sports and the 2 groups of health conditions (PA-SCI and PA-LLA). In conclusion, PA-LLA had a higher cardiometabolic risk, whereas PA-SCI-H had a higher platelet-derived cardiovascular risk. Further larger studies are needed to investigate the relationship between indexes of inflammation/oxidation and dietary habit, body composition, and physical fitness/performance in PA with motor impairments., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2019 Marco Bernardi et al.)

There are still unknown mechanisms involved in the development of Parkinson's disease (PD), which elucidating them can assist in developing efficient therapies. Recently, studies showed that genes located on the human chromosomal location 22q11.2 might be involved in the development of PD. Therefore, the present study was designed to evaluate the role of two genes located on the chromosomal location (miR-185 and SEPT5), which were the most probable candidates based on our bibliography. In vivo and in vitro models of PD were developed using male Wistar rats and SHSY-5Y cell line, respectively. The expression levels of miR-185, SEPT5, LRRK2, and PARK2 genes were measured at a mRNA level in dopaminergic areas of rats' brains and SHSY-5Y cells using the SYBR Green Real-Time PCR Method . Additionally, the effect of inhibition on the genes or their products on cell viability and gene expression pattern in SHSY-5Y cells was investigated. The level of miR-185 gene expression was significantly decreased in the substantia nigra (SN) and striatum (ST) of the rotenone-treated group (control group) compared to the healthy normal group ( P < 0.05). In addition, there was a significant difference in the expression of SEPT5 gene ( P < 0.05) in the substantia nigra between two studied groups. The results of an in vitro study showed no significant change in the expression of the genes; however, the inhibition on miR-185 gene expression led to the increase in LRRK2 gene expression in SHSY-5Y cells. The inhibition on LRRK2 protein also decreased the cellular toxicity effect of rotenone on SHSY-5Y cells. The results suggested the protective role of miR-185 gene in preventing the development of PD., Competing Interests: On behalf of all the authors, the corresponding author states that there is no conflict of interest., (Copyright © 2019 Arman Rahimmi et al.)

Neutrophil-to-lymphocyte ratio (NLR) has been proposed as a bone loss index in postmenopausal women and as a marker of inflammation in coeliac patients. The aims of this work were to evaluate the effect of gluten-free diet (GFD) on NLR retrospectively and study the relationship between NLR and Mediterranean diet adherence and selected food groups (fruits, vegetables, red meat, potatoes, and unrefined and refined cereals). Adult individuals ( n = 50), who had been on a strict GFD by at least 6 months, were recruited. The degree of adherence to the Mediterranean diet was calculated with two different scores: the Mediterranean Diet Score (MDS-14), assessed through the validated 14-item questionnaire of the PREDIMED study, and the MEDScore (Score-55) proposed by Panagiotakos. The latter includes the consumption of unrefined cereals (UC). High percentages of osteopenia and osteoporosis were found within the recruited subjects, who furnished the reports of bone mineral density (BMD), in particular in postmenopausal (Post-M) women. Recent NLR was higher in subjects with osteoporosis compared to osteopenia and normal BMD. However, retrospective analysis showed both increase and decrease in NLR after GFD, with no significant differences between Marsh grade, anemia, and BMD status. Moreover, premenopausal previous pregnancy (Pre-MPP) and Post-M had higher NLR at diagnosis compared to Men and premenopausal (Pre-M), but higher differences were observed in recent NLR between Pre-MPP and Men only. Chocolate consumption was associated with lower recent NLR, whereas the latter was correlated with Score-55, but not with MDS-14. Moreover, refined cereal consumption was correlated with recent NLR. Although large prospective studies are needed in order to clarify the relationship between UC and NLR in coeliac patients, in this pilot study, we have investigated for the first time the relationship between NLR, dietary habit, and osteoporosis in coeliac disease.

Background: The life of patients with β -thalassemia major depends on blood transfusion. Regular blood transfusion leads to hemosiderosis in their main organs. The aim of this study was to compare the effects of deferasirox and deferoxamine on renal damage in patients with β -thalassemia major., Method: The present case-control study was conducted on 60 individuals who were referred to the 17th Shahrivar Tertiary Referral Hospital in Guilan province, Iran. In this study, patients with β -thalassemia major who used deferasirox ( n = 21) and patients who used deferoxamine ( n = 19) were evaluated. The control group ( n = 20) was selected from healthy individuals. Serum creatinine (CREA), blood urea nitrogen (BUN), and Cystatin C were measured from blood samples. Furthermore, urinary (U.) neutrophil gelatinase-associated lipocalin (NGAL), albumin (Alb), interleukin- (IL-) 18, and Kidney Injury Molecule-1 (KIM - 1) were measured by the ELISA method and normalized for U. creatinine (CREA)., Results: U. NGAL, U. IL-18, and BUN biomarkers in the deferasirox group were significantly higher than those in the control group ( p < 0.001). U. NGAL/CREA and U. KIM-1/CREA ratios increased in both the deferoxamine and deferasirox groups compared to the control group ( p < 0.05). U. Alb was significantly higher in patients treated with deferoxamine than in healthy participants ( p < 0.05)., Conclusion: The findings of this study indicate that after taking deferasirox, there was renal damage and an increase in inflammatory factors. Also, minor renal impairment was observed after deferoxamine administration, but it was not confirmed at the molecular level (U. NGAL and KIM-1). Therefore, it seems that patients who are taking these two drugs should be monitored carefully.

Alkaloids are among the natural phytochemicals contained in functional foods and nutraceuticals and have been suggested for the prevention and/or management of oxidative stress and inflammation-mediated diseases. In this review, we aimed to describe the effects of alkaloids in angiogenesis, the process playing a crucial role in tumor growth and invasion, whereby new vessels form. Antiangiogenic compounds including herbal ingredients, nonherbal alkaloids, and microRNAs can be used for the control and treatment of cancers. Several lines of evidence indicate that alkaloid-rich plants have several interesting features that effectively inhibit angiogenesis. In this review, we present valuable data on commonly used alkaloid substances as potential angiogenic inhibitors. Different herbal and nonherbal ingredients, introduced as antiangiogenesis agents, and their role in angiogenesis-dependent diseases are reviewed. Studies indicate that angiogenesis suppression is exerted through several mechanisms; however, further investigations are required to elucidate their precise molecular and cellular mechanisms, as well as potential side effects.

High intakes of vegetables have been associated with a lower incidence of cardiovascular diseases (CVD). However, the effect of vegetables on immune function and antioxidant status in human studies have provided contrasting results. In the present study, after a week of run-in period, 38 subjects at risk of CVD were randomly assigned to one of the following 4-week interventions: low vegetable consumption (800 g of vegetables/week) or high vegetable consumption (4200 g of vegetables/week). Vegetables included carrots, topinambur (Jerusalem artichoke, Helianthus tuberosus ), tomatoes, red cabbage, and sweet peppers. Blood and salivary samples were collected before and after intervention periods. In addition to clinical, immunological, and antioxidant markers, leukocyte and lymphocyte expression of the gut-homing β 7 integrin was evaluated. No significant changes were detected in clinical, immunological, and antioxidant markers in biological samples, except for an increase in white blood cell count for the low vegetable consumption group ( p < 0.05). The study provides additional evidence about the uncertainty of providing a clear evidence for vegetables in modulating markers of immune function and antioxidant status. Further studies are needed in order to unravel the mechanism of effect of vegetable consumption in cardiovascular prevention.

Vegetables and fruits contain non-provitamin A (lycopene, lutein, and zeaxanthin) and provitamin A ( β -carotene, β -cryptoxanthin, and α -carotene) carotenoids. Within these compounds, β -carotene has been extensively studied for its health benefits, but its supplementation at doses higher than recommended intakes induces adverse effects. β -Carotene is converted to retinoic acid (RA), a well-known immunomodulatory molecule. Human interventions suggest that β -carotene and lycopene at pharmacological doses affect immune functions after a depletion period of low carotenoid diet. However, these effects appear unrelated to carotenoids and retinol levels in plasma. Local production of RA in the gut-associated lymphoid tissue, as well as the dependency of RA-induced effects on local inflammation, suggests that personalized nutrition/supplementation should be considered in the future. On the other hand, the differential effect of RA and lycopene on transforming growth factor-beta suggests that lycopene supplementation could improve immune functions without increasing risk for cancers. However, such preclinical evidence must be confirmed in human interventions before any recommendations can be made.

Oxidative stress is the result of the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1) ROS in leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced modifications of lipids, DNA, and proteins, (3) enzymatic players of redox status, and (4) total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.

The highly nutritional and ecofriendly Spirulina ( Arthrospira platensis ) has hypolipidemic, hypoglycemic, and antihypertensive properties. Spirulina contains functional compounds, such as phenolics, phycocyanins, and polysaccharides, with antioxidant, anti-inflammatory, and immunostimulating effects. Studies conducted on Spirulina suggest that it is safe in healthy subjects, but attitude to eating probably affects the acceptability of Spirulina containing foods. Although the antioxidant effect of Spirulina is confirmed by the intervention studies, the concerted modulation of antioxidant and inflammatory responses, suggested by in vitro and animal studies, requires more confirmation in humans. Spirulina supplements seem to affect more effectively the innate immunity, promoting the activity of natural killer cells. The effects on cytokines and on lymphocytes' proliferation depend on age, gender, and body weight differences. In this context, ageing and obesity are both associated with chronic low grade inflammation, immune impairment, and intestinal dysbiosis. Microbial-modulating activities have been reported in vitro, suggesting that the association of Spirulina and probiotics could represent a new strategy to improve the growth of beneficial intestinal microbiota. Although Spirulina might represent a functional food with potential beneficial effects on human health, the human interventions used only supplements. Therefore, the effect of food containing Spirulina should be evaluated in the future., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Despite tea increased plasma nonenzymatic antioxidant capacity, the European Food Safety Administration (EFSA) denied claims related to tea and its protection from oxidative damage. Furthermore, the Supplement Information Expert Committee (DSI EC) expressed some doubts on the safety of green tea extract (GTE). We performed a pilot study in order to evaluate the effect of a single dose of two capsules of a GTE supplement (200 mg × 2) on the peroxidation of leukocytes index ratio (PLIR) in relation to uric acid (UA) and ferric reducing antioxidant potential (FRAP), as well as the sample size to reach statistical significance. GTE induced a prooxidant effect on leukocytes, whereas FRAP did not change, in agreement with the EFSA and the DSI EC conclusions. Besides, our results confirm the primary role of UA in the antioxidant defences. The ratio based calculation of the PLIR reduced the sample size to reach statistical significance, compared to the resistance to an exogenous oxidative stress and to the functional capacity of oxidative burst. Therefore, PLIR could be a sensitive marker of redox status., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

For the first time, we investigated the relationship between postprandial dysmetabolism and the Peroxidation of Leukocytes Index Ratio (PLIR), a test that measures the resistance of leukocytes to exogenous oxidative stress and their functional capacity of oxidative burst upon activation. Following a blind, placebo controlled, randomized, crossover design, ten healthy subjects ingested, in two different occasions, a high fat and high carbohydrates meal with Snello cookie (HFHCM-S) or with control cookies (HFHCM-C). Snello cookie, a functional food covered by dark chocolate and containing glucomannan, inulin, fructooligosaccharides, and Bacillus coagulans strain GanedenBC30, significantly improved postprandial metabolic stress (insulin, glucose, and triglycerides) and reduced the postprandial increase of uric acid. HFHCM-S improved PLIR of lymphocytes, but not of monocytes and granulocytes. Both meals increased granulocytes' count and reduced the lipoperoxidation induced by both exogenous free radicals and reactive oxygen species (ROS) produced by oxidative burst. Our results suggest that the healthy status of the subjects could be a limitation of this pilot study for PLIR evaluation on cells that produce ROS by oxidative burst. In conclusion, the relationship between PLIR and postprandial dysmetabolism requires further investigations.