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Abstract: Cetirizine is a second generation histamine H1 receptor antagonist used to provide symptomatic relief of allergic signs caused by histamine release. The aim of the study was to learn whether the survival and the motor incoordination (ataxia) side effect of cétirizine administration is dosing time-dependent. Materials and methods. – A total of 240 male Swiss mice, 10 weeks of age were synchronized for 3 weeks by 12 h light (rest span)/12 h dark (activity span). Different doses of cetirizine were administered orally at fixed times during the day to determine both the sublethal (TD50) and lethal (LD50) doses, which were, respectively, 55 ± 0.35 and 750 ± 0.40 mg/kg. In the chronotoxicologic study a single dose of cétirizine (DL50) was administered to comparable groups of animals at six different circadian stages [1, 5, 9, 13, 17, 21 h after light onset (HALO)]. Results. – The survival was statistically significant dosing time-dependent (χ2 = 16.73; P < 0.001). Drug dosing at 17 HALO resulted in 83.3% survival rate whereas drug dosing at 5 HALO was only 23.25%. Cosinor analysis revealed a statistically significant circadian (period ≈ 24 h) rhythmic component in survival. Lowest (20%) and highest (88%) ataxia occurred when cetirizine was administered, respectively, at 17 and 5 HALO. Cosinor analysis revealed a statistically significant circadian (period ≈ 24 h) rhythmic component in ataxia. Conclusion. – Our results reveal that the best safety is shown when cetirizine is administered in the middle of the dark (activity) span of the mice, since it produces some side effects: ataxia and hyperthermia. Taking into account of the hour administration of cetirizine, improves treatment efficacy and permit the best control of allergic diseases. [Copyright &y& Elsevier]

The nasal angiocentric T-cell-natural killer cell lymphoma is an aggressive tumor, exceptional in Tunisia, which is observed especially in Asia, Mexico and South America. We report the case of an 11-year-old boy, presenting with an exuberant and ulcerative tumor of the right nasal pit. Radiological investigation evidenced a right ethmoi¨do-frontal tumor. Evolution was characterized by the installation of abdominal pain and fever, the evidenciation of a mass within the head of the pancreas that compressed the extra hepatic biliary duct and Wirsung’s canal and was associated to hyperamylasemia. Biopsy under ultrasound revealed a histiocytic nature. Nasal biopsy found histiocytic and lymphocytic cells and led to a diagnosis of rhinoscleroma. The absence of improvement under antibiotic treatment and the development of fever with leuconeutropenia oriented towards the diagnosis of a non-Hodgkinian malignant lymphoma. Medullary biopsy and immunohistochimic study confirmed a T/NK cells lymphoma, with medullary invasion. The child died from acute respiratory distress syndrome. The authors insist on the rarity of this bipolar location, in particular in children, emphasize the difficulty of the diagnosis and review the literature. [Copyright &y& Elsevier]

The increased production of reactive oxygen species (ROS) by human neutrophils can lead to oxidative imbalances and several diseases, such as inflammatory bowel disease (IBD). Opuntia ficus-indica (O. ficus-indica) is rich in bioactive substances with anti-inflammatory properties. This study aimed to identify the bioactive compounds present in aqueous cladodes extract (ACE) of O. ficus-indica using high-performance liquid chromatography (HPLC) and to test its effects on human neutrophil inflammatory functions and on ulcerative colitis (UC) induced by acetic acid (Aa) in rats. ROS production and degranulation by neutrophils were assessed by luminol-amplified chemiluminescence, enzymatic techniques, and western blotting. In vivo, the experiment involved seven groups of rats: a negative control group (NaCl), the acetic acid group (Aa), and groups treated with oral sulfasalazine (150 mg/kg) or various doses of ACE for 7 days. Colonic lesions were induced by an intra-rectal Aa injection, and inflammation was assessed. HPLC analysis identified gallic acid, catechin, caffeic acid, and ferulic acid as major compounds in ACE. In vitro, ACE inhibited neutrophil ROS production, including superoxide anion produced by NADPH oxidase, and significantly reduced myeloperoxidase activity and neutrophil degranulation. In vivo, ACE protected rats from Aa-induced histopathological damage of the colonic mucosa, significantly increased catalase, superoxide dismutase and reduced glutathione levels, and significantly suppressed the increases of plasma cytokines (TNF-α and IL-1β) observed in the Aa group. In conclusion, O. ficus-indica ACE has significant anti-inflammatory properties by restoring oxidative balance, indicating that it could be a potential source of therapeutic agents for inflammatory diseases, particularly UC., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Plants of the genus Tribulus have been used in folk medicine for wound healing, alleviating liver, stomach, and rheumatism pains, and as cognitive enhancers, sedatives, antiseptics, tonics, and stimulants. The present work aimed to evaluate whether Tribulus terrestris (Tt) administered for 15 days attenuated cognitive deficits and exhibited anxiolytic and antidepressant profiles in scopolamine-induced amnesia in zebrafish. Animals were randomly divided into six groups (eight animals per group): (1)-(3) Tt treatment groups (1, 3 and 6 mg/L), (4) control, (5) scopolamine (SCOP, 0.7 mg/kg), and (6) galantamine (Gal, 1 mg/L). Exposure to SCOP (100 µM) resulted in anxiety in zebrafish, as assessed by the novel tank diving test (NTT) and novel approach test (NAT). When zebrafish were given SCOP and simultaneously given Tt (1, 3, and 6 mg/L once daily for 10 days), the deficits were averted. Molecular interactions of chemical compounds from the Tt fractions with the monoamine oxidase A (MAO-A) were investigated via molecular docking experiments. Using behavioral experiments, we showed that administration of Tt induces significant anxiolytic-antidepressant-like effects in SCOP-treated zebrafish. Our result indicated that flavonoids of Tt, namely kaempferol, quercetin, luteolin, apigetrin, and epigallocatechin, could act as promising phytopharmaceuticals for improving anxiety-related disorders.

Tribulus terrestris L. (Tt) has been recently gaining attention for its pharmacological value, including its neuroprotective activities. In this study, we explore the neuroprotective effects of a Tribulus terrestris extract in a zebrafish ( Danio rerio ) model of scopolamine (SCOP)-induced memory impairment and brain oxidative stress. SCOP, an anticholinergic drug, was employed to replicate fundamental aspects of Alzheimer's disease (AD) in animal models. The fish were treated with ethanolic leaf extract (ELE) from Tt (1, 3, and 6 mg/L) for 15 days. SCOP (100 µM) was administered 30 min before behavioral tests were conducted. Molecular interactions of the major compounds identified via UPLC-PDA/MS in Tt fractions with the active site of acetylcholinesterase (AChE) were explored via molecular docking analyses. Terrestrosin C, protodioscin, rutin, and saponin C exhibited the most stable binding. The spatial memory performance was assessed using the Y-maze test, and memory recognition was examined using a novel object recognition (NOR) test. Tt extract treatment reversed the altered locomotion patterns that were caused by SCOP administration. Biochemical analyses also verified Tt's role in inhibiting AChE, improving antioxidant enzyme activities, and reducing oxidative stress markers. The present findings pave the way for future application of Tt as a natural alternative to treat cognitive disorders.

Ulcerative colitis is an inflammatory bowel disease with a complex aetiology characterised by abnormal immune responses and oxidative stress-induced tissue injury. Inflammatory cells play an important role in the progression of this pathology through the overproduction of reactive oxygen species (ROS) from various sources including the NADPH oxidases (NOXs). The aim of this study was to investigate the preventive effect of apocynin, a natural antioxidant molecule and a selective inhibitor of NOXs, on acetic acid (AA)-induced ulcerative colitis in rats. Our results first confirmed that apocynin has a high free radical scavenging capacity as well as a potent iron chelating ability. Oral pretreatment of rats with apocynin (200 mg/kg and 400 mg/kg) for 7 days prior to AA-induced colitis suppressed the increase in pro-oxidant markers in colonic homogenates and preserved colonic cytoarchitecture from acetic acid-induced damage. Oral administration of apocynin (200 mg/kg and 400 mg/kg) also reduced several systemic inflammatory markers such as alkaline phosphatase, iron, pro-inflammatory cytokines, C-reactive protein and myeloperoxidase. This study shows that apocynin protects rats from acetic acid-induced colonic inflammation and suggests that apocynin may have a promising beneficial effect in the prevention of ulcerative colitis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study investigates the seasonal variations of physiological responses, milk yield, milk composition, and milk fatty acid profile of local crossbred cows (Friesian × Brown Atlas) in northwestern Tunisia. A total of 80 multiparous cows from smallholder farmers were sampled between 2018 and 2019. The cows were feed the same diet ad libitum and exposed to the same Mediterranean climatic conditions. Weekly rectal temperature (RT; °C), respiratory rate (RR; rpm), and heart rate (HR; bpm) were measured per cow in each season. Individual milk yield and samples were recorded bi-weekly and collected in duplicate for chemical analyses. Milk fatty acids (FAs) were analyzed using gas chromatography-mass spectrometry (GC-MS). Results showed an increase (P < 0.05) in RT (+ 1.3%), RR (+ 12.1%), and HR (+ 9.9%) when the temperature-humidity index (THI) increased from winter (53.6) to summer (74.4) in response to heat stress. Milk yield did not vary significantly between seasons (8.3 L/day on average). Summer milk contained more fat (+ 7.8%) and log SCC (+ 13.7%). The proportion of the monounsaturated (31.2 vs. 27.2%) and polyunsaturated (4.29 vs. 3.86%) FAs decreased (P < 0.05) between winter and summer. Saturated FAs (64.5 vs. 67.7%) were higher (P < 0.05) in summer than in winter. Winter milk fat contained higher levels of C18:2cis-9 trans-11 (CLA) (0.73 vs. 0.56%) and ω-3 FA (0.83 vs. 0.63%), but a lower ω-6/ω-3 ratio (4.07 vs. 6.17%) compared to summer. As the cows were fed the same diet throughout the two seasons, the performances obtained were mainly due to the resistance of the local crossbred cow to the hot conditions. It is concluded that the local crossbred cow maintains its productivity and tolerate the hot Mediterranean climate., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Melia azedarach L., a Meliaceae family tree, is widely used in traditional folkloric medicine for its pharmaceutical properties. In the present study, we investigated the phytochemical composition of four methanolic leaf extracts of M. azedarach of various origins (Algeria and Tunisia) using high-performance liquid chromatography (HPLC). The antibacterial efficacy and mechanisms of action against Gram-positive and Gram-negative pathogenic microorganisms were then evaluated. Our findings revealed a presence of phenolic acids and flavonoids, such as gallic acid, chlorogenic acid, caffeic acid, hyperoside, isoquercetin, quercetin, and isorhamnetin both in Algerian and Tunisian localities, with an abundance of phenolic acids compared to flavonoids. Additionally, the studied extracts exhibit a broad spectrum of antibacterial activities, with MIC values ranging from 31.25 mg/mL to 125 mg/mL. Methanolic leaf extracts of M. azedarach from Algeria exhibited more potent biofilm eradication, with a percentage of inhibition reaching 72.17% against the S. aureus strain. Furthermore, inhibitory concentrations of tested substances, particularly the extract from the Relizane area, were capable of disrupting the membrane integrity of the treated bacteria as well as producing oxidative stress through ROS generation. Likewise, our results reveal that plant extract induces lipid peroxidation by raising MDA levels in comparison to untreated cells, particularly with the plant extract of Blida. M. azedarach extracts also reduced the synthesis of antioxidant enzymes (CAT and SOD). Our findings illustrate that M. azedarach remains a plant with significant antibacterial potential and distinct mechanisms of action that are closely related to the origins of this specimen.

The present study was conducted to investigate the chemical composition of Ailanthus altissima (Mill.) Swingle methanolic leaf extracts from geographically distinct regions and to assess their antimicrobial properties along with their ability to induce oxidative stress. The HPLC-DAD analysis revealed the presence of phenolic acids and flavonoids including chlorogenic acid, gallic acid, synapic acid, p-coumaric acid, apigenin, hyperoside, isoamnétine-3-O-beta-D-glucotrioside, quercetin, and isoquercetin in various amounts depending on the origin of tested extracts. The assessment of antibacterial activity showed the effectiveness of the A. altissima extracts particularly against Gram-positive bacteria, with inhibition zone diameters reaching 14 ± 1 mm and minimum inhibitory concentrations ranging from 4 to 72.2 mg/mL. These bioactive substances also exhibited strong antibiofilm activity with an eradication percentage reaching 67.07%. Furthermore, they increased ROS production to levels two to five times higher than the control group, altered the membrane integrity and caused lipid peroxidation with MDA production exceeding 2.5 µmol/mg protein in the Gram-positive and Gram-negative strains. A decrease in the levels of the antioxidant enzymes SOD and CAT was also observed, indicating an impairment of the bacterial response to the oxidative stress caused by the tested extracts. These findings highlight the antibacterial properties of A. altissima leaf extracts depending on their origins and promote their exploitation and application in the agro-food and pharmaceutical sectors.

Vitis vinifera leaves (VVL) are agro-industrial waste. In the current study, the phytochemical profile of V. vinifera leaves extracts (VVLE) of two Tunisian autochthonous accessions was determined via LC-UV-ESI/MS, and their antioxidant and hepatoprotective properties were also assessed. Mice were pretreated orally with VVLE (7.5, 15 and 30 mg/kg) for 7 days, and then received acutely and by i.p. a solution CCl 4 at 12% in sunflower oil (v/v). Serum levels of hepatic markers, oxidative stress indicators in liver tissue and histological changes were assessed. LC-UV-ESI/MS analysis revealed four phenolic compounds identified in both extracts with quercetin-3- O -glucuronide being the dominant constituent (23.32 ± 1.06 vs. 10.24 ± 0.12 mg/g DM, p < 0.05 for wild and cultivated accessions, respectively). The Antioxidant activity revealed a significant difference between the genotypes. Moreover, the VVLE of the wild "Nefza-I" ecotype was the most active based on antioxidant assays. Furthermore, the results showed that pre-treatment, especially with VVLE, of the wild ecotype "Nefza-I", attenuated CCl 4 -induced acute liver injury in a dose-dependent manner, as demonstrated by the decrease in the activities of hepatic serum function markers. This was also evidenced by a decrease in the levels of lipoperoxidation and histological damage in the liver, as well as a restoration of antioxidant enzyme activities (SOD and catalase) and an increase in the hepatic glutathione content. Our results demonstrate that VVLE possesses protective effects on CCl 4 -induced liver injury. Overall, the wild ecotype "Nefza-I" extract could serve as an effective protector against CCl 4 -induced hepatocellular oxidative stress., Competing Interests: 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., (© 2023 Published by Elsevier Ltd.)

Inflammation is the body's response to insults, for instance, lung inflammation is generally caused by pathogens or by exposure to pollutants, irritants and toxins. This process involves many inflammatory cells such as epithelial cells, monocytes, macrophages and neutrophils. These cells produce and release inflammatory mediators such as pro-inflammatory cytokines, lipids and reactive oxygen species (ROS). Lung epithelial cells and phagocytes (monocytes, macrophages and neutrophils) produce ROS mainly by the NADPH oxidase NOX1 and NOX2, respectively. The aim of this study was to investigate the effects of two NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI), on lipopolysaccharide (LPS)-induced lung inflammation in rats. Our results showed that apocynin and DPI attenuated the LPS-induced morphological and histological alterations of the lung, reduced edema and decreased lung permeability. The evaluation of oxidative stress markers in lung homogenates showed that apocynin and DPI inhibited LPS-induced NADPH oxidase activity, and restored superoxide dismutase (SOD) and catalase activity in the lung resulting in the reduction in LPS-induced protein and lipid oxidation. Additionally, apocynin and DPI decreased LPS-induced MPO activity in bronchoalveolar liquid and lung homogenates, TNF-α and IL-1β in rat plasma. NADPH oxidase inhibition could be a new therapeutic strategy for the treatment of inflammatory lung diseases.

Introduction: Chronic kidney disease (CKD) is a worldwide public health concern characterised by a progressive alteration of renal function, and obesity, diabetes and hypertension are major risk factors. Oxidative stress is commonly observed in CKD patients resulting from an imbalance between overproduction of reactive oxygen species (ROS) and impairment of defense mechanisms. Therefore, strategies that alleviate oxidative stress may have major clinical implications towards improving vascular health and reducing the burden of CKD. Also, CKD worsens the quality of life of patients, therefore it is fundamental to implement new therapeutic strategies aimed at slowing down its progression., Materials and Methods: This interventional study is a randomised placebo-controlled clinical trial consisting at the daily oral supplementation with high dosing grape seed flour (GSF ≈ 1 g/kg) for experimental (n = 30) or starch for placebo (n = 10) to patients suffering from CKD of various stages and aetiologies. Blood and urine samples were collected at baseline and after a six-month-long supplementation period to follow up the disease evolution through the determination of renal function biomarkers, as well as antioxidant, anti-inflammatory and blood parameters., Results: Supplementation with high dosing GSF was safe and well tolerated during the entire period of investigation. GSF clearly improved the main renal function biomarkers as GFR, proteinuria, blood pressure, oxidative stress and inflammation as well as the overall patient welfare as indicated by several blood parameters., Conclusion: Most importantly high dosing GSF specifically halted and even reversed the progression of diabetic nephropathy a major cause of CKD and end stage renal disease.

Anti-leishmanial drugs extracted from natural sources have not been sufficiently explored in the literature. Until now, leishmaniasis treatments have been limited to synthetic and expensive drugs. This study investigated, for the first time, the anti-leishmanial efficacy of essential oils (EOs) from the leaves of Citrus species ( C. sinensis , C. limon , and C. clementina ). Essential oils were extracted from three species by solvent free microwave extraction (SFME); in addition, lemon oil was also isolated by hydro-distillation (HD). These were investigated using gas chromatography coupled with mass spectrometry (GC-MS) and evaluated against Leishmania species, namely Leishmania major and Leishmania infantum , using a mitochondrial tetrazolium test (MTT) assay. The chemical compositions of Citrus limon EOs obtained by HD and SFME showed some differences. The identified peaks of C. limon (SFME) represented 93.96%, where linalool was the major peak (44.21%), followed by sabinene (14.22%) and ocimene (6.09%). While the hydro-distilled oil of C. limon contained geranial (30.08%), limonene (27.09%), and neral (22.87%) in the identified peaks (96.67%). The identified components of C. clementina leaves oil (68.54%) showed twenty-six compounds, where the predominant compound was geranial (42.40%), followed by neral (26.79%) and limonene (14.48%). However, 89.82% C. sinensis oil was identified, where the major peaks were for neral (27.52%), linalool (25.83%), and geranial (23.44%). HD oil of lemon showed the highest activity against L. major , with moderate toxicity on murine macrophage (RAW 264.7) cells, and possessed the best selectivity index on both Leishmanial species (SI: 3.68; 6.38), followed by C. clementina oil and C. limon using SFME (0.9 ± 0.29, 1.03 ± 0.27, and 1.13 ± 0.3), respectively. C. clementina oil induced the greatest activity on Leishmania infantum , followed by HD lemon and SFME lemon oils (0.32 ± 0.18, 0.52 ± 0.15, and 0.57 ± 0.09, respectively) when compared to Amphotericin B (0.80 ± 0.18 and 0.23 ± 0.13) as a positive control, on both species, respectively. Our study suggests a potent anti-leishmanial activity of lemon oil (HD) on L. major , followed by C. clementina . With the same potency on L. infantum shown by C. clementina oil, followed by HD lemon oil. This effect could be attributed to the major compounds of limonene, citral, and neral, as well as the synergistic effect of other different compounds. These observations could be a starting point for the building of new anti-leishmanial drugs from natural origins, and which combine different EOs containing Citrus cultivars.

According to the free-radical theory of aging, accumulation of reactive oxygen species (ROS) within mitochondria throughout life span leads to impairment of the main biological macromolecules as DNA, lipids, and proteins, which might be at the basis of premature aging. One way to test experimentally such a hypothesis consists in intervention studies using antioxidant nutrients aimed at limiting or inhibiting ROS production that should be able to reduce the aging rate and disease pathogenesis. Grape seed flour (GSF) contains a high level of phytochemicals among which bioactive polyphenols exhibit numerous biological properties and beneficial health effects as antioxidant, anti-inflammatory, anticarcinogenic, multi-organ (heart, liver, kidney, and brain among others) protective. The present study aimed at testing the ability of high dosing GSF (4 g/kg bw) used as a nutritional supplement to slow down aging and prolong life span of Wistar rats when administered from early life (1-month-old animals) till their natural death. Data clearly show that high-dose GSF extends organism longevity and health span by improving multi-organ damages, systemic fueling metabolism declines, and alleviated oxidative stress and inflammation in aging rats. Our data support the extending longevity effect of grape polyphenols especially when used as high dosing nutritional supplement or as natural medicine whose appropriate galenic form as solid lipid nanoformulation is currently under investigation., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In Mediterranean forests, anthropogenic disturbances received little interest in regards to their shrub layer induced enlargement. We studied in the cork oak forest of Beni Métir and in undisturbed and disturbed sites, the relative contribution of the tree (L T , DL T ) and shrub (L S , DL S ) layers to litter fall, litter decomposition, and nutrients dynamic. Our results showed that disturbance significantly (p < 0.001) reduced (-43%) total litter fall in DS in comparison with S (583 g m -2 year -1 ); the increased (+ 54%) shrub layer contribution to site litter fall did not counterbalance the decreased input by the tree layer. Leaf litter decomposition was negatively affected (p < 0.001) by disturbance, the remaining mass value being after 2 years, approximately 14 and 33%, respectively, for S and DS. This resulted into a gain of above ground soil organic matter 1.3 higher in DS than it was in S whereas the shrub layer contribution to litter fall increased by 50%. The prevailing driver of decomposition was very probably not related to litter quality but rather site-dependent. Indeed, layers of the same site shared the same remaining mass in spite of significant differences (p < 0.05) in initial content of minerals (N, Ca, and Mn) implicated in biological decomposition. In the disturbed site, the nutrient input by the shrub layer increased by more than double, but its low nutrient quality drastically impaired litter decomposition and mineral return at the site level. In conclusion, this study highlighted the importance of shrub layer which must be taken into account when considering any disturbance assessment and management of Mediterranean forests., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lupin seeds can represent a valuable source of phenolics and other antioxidant compounds. In this work, a comprehensive analysis of the phytochemical profile was performed on seeds from three Lupinus species, including one cultivar ( Lupinus albus ) and two wild accessions ( Lupinus cossentinii and Lupinus luteus ), collected from the northern region of Tunisia. Untargeted metabolomic profiling allowed to identify 249 compounds, with a great abundance of phenolics and alkaloids. In this regard, the species L. cossentinii showed the highest phenolic content, being 6.54 mg/g DW, followed by L. luteus (1.60 mg/g DW) and L. albus (1.14 mg/g DW). The in vitro antioxidant capacity measured by the ABTS assay on seed extracts ranged from 4.67 to 17.58 mg trolox equivalents (TE)/g, recording the highest values for L. albus and the lowest for L. luteus . The DPPH radical scavenging activity ranged from 0.39 to 3.50 mg TE/g. FRAP values varied between 4.11 and 5.75 mg TE/g. CUPRAC values for lupin seeds ranged from 7.20 to 8.95 mg TE/g, recording the highest for L. cossentinii . The results of phosphomolybdenum assay and metal chelation showed similarity between the three species of Lupinus . The acetylcholinesterase (AChE) inhibition activity was detected in each methanolic extract analyzed with similar results. Regarding the butyrylcholinesterase (BChE) enzyme, it was weakly inhibited by the Lupinus extracts; in particular, the highest activity values were recorded for L. albus (1.74 mg GALAE/g). Overall, our results showed that L. cossentinii was the most abundant source of polyphenols, consisting mainly in tyrosol equivalents (5.82 mg/g DW). Finally, significant correlations were outlined between the phenolic compounds and the in vitro biological activity measured, particularly when considering flavones, phenolic acids and lower-molecular-weight phenolics.

Genetic diversity and differences among durum-wheat cultivars evolved in various regions of the world are important for sustainable production in the current climate change scenario. Information regarding genetic differences was also important for the correct choice of parental material for the selection of high quality cultivars. Two elite and six obsolete cultivars of durum-wheat were characterized with 25-simple sequence repeats (SSR) markers. All accessions were evaluated for 2-agronomic-traits (Yield (Y) and Thousand-Kernel-Weight (TKW)) and 11 grain quality-traits (grain protein content (GPC), grain moisture contents (H), carotene content (CT), sedimentation test (SDS), gluten content (GC), gluten index (GI), semolina color index (L*, a*, b*) and alveographic parameters (W and P/L)) under randomized complete block design with three replication for two crop seasons (2015-2017). Genetic characterization through SSR markers revealed 126 alleles with an average of 5.04 alleles locus-1 and had average 0.79 polymorphism information content (PIC). The comparisons revealed that elite accessions were more productive in terms of grain yield and TKW, whereas obsolete accessions showed high GPC and end-use quality-traits. The generated dendrogram based on SSR markers, agronomic, seed quality-traits clearly differentiate the genotypes in two main groups obsolete and elite accessions. Analysis of correlation revealed a significant association between the traits TKW, Y, b*, a*, GPC, GC, SDS and H. High genetic diversity found between elite and obsolete cultivars for parameters such as yield, end-use quality and their correlation with SSR markers could help breeders for an eventual breeding program on durum-wheat.

Enteropathogenic Escherichia coli E2346/69 (EPEC) has caused foodborne outbreaks worldwide and the bacterium forms antimicrobial-tolerant biofilms. The anti-biofilm formation of various components of essential oils extracted from selected medicinal plants were investigated and tested on EPEC and wild strains of E. coli . Oils extracted from the family Asteraceae and their major common constituents at 0.031 and 0.062% (V/v) were found to significantly inhibit biofilm formation without affecting the growth of planktonic cells. In addition, three plants belonging to this family ( Artemisia herba alba , Artemisia campestris and Artemisia absinthium ) played important roles in the antimicrobial activity. Interestingly, their essential oils reduced the ability of E . coli (the EPEC and K12 strains) to form a biofilm. The crystal violet reduction assay showed that the plant extracts tested reduced biofilm formation with the inhibition of bacterial attachment up to 45% for EPEC and 70% for E. coli K-12 after 24 h treatment at 0.62 mg ml -1 , demonstrating that Artemisia oils had a high anti-biofilm activity on the bacteria tested. The results indicate that the locus of enterocyte effacement (LEE) acquired by horizontal transfer promotes the formation of the attaching and effacing (A/E) lesion and increases the capacity of the photogen strain (EPEC) to form a biofilm. The chemical composition of the volatile compounds was obtained by gas chromatography-mass spectrometry analysis, which showed that the essential oils consisted of thirty-four compounds. Chamazulene (39.21%), β-pinene (32.07%), and α-thujone (29.39%) were the main constituents of the essential oils of A. herba alba , A. absinthium and A. campestris, respectively.

Context: Vitis vinifera leaves are traditionally used in Tunisian folk medicine to treat digestive pathologies. Objective: We aimed to compare the gastroprotective effects of hydromethanolic leaves extracts of wild and cultivated grapes accessions native of Tunisia. Materials and methods: The phytochemical analysis of grapevine leaves extracts was performed. The gastroprotective activity was evaluated by ethanol-induced gastric-ulcer in rats pre-treated with increased doses of the extracts or with the standard omeprazole. Index of gastric secretions (volume, pH and gastric mucus production), stomach wall histology and biochemical parameters were estimated for assessment of anti-secretory and gastroprotective effects of the extracts. Results: Pre-treatment with grapevine leaves extracts decreased significantly gastric volume, gastric mucosal damage and increased significantly gastric juice pH compared with the negative control group. The extracts prevented ethanol-induced decrease of the activity of antioxidant enzymes while the levels of malondialdehyde and of reduced glutathione were decreased significantly. Moreover, the most marked effect was observed at low doses of wild ecotype 'Nefza-I' extracts. Conclusion: The leaves of Vitis species might be suitable as a functional food for therapeutic purpose and demonstrates gastroprotective action in gastric lesions model. Both accessions exhibited gastroprotective effects, but wild 'Nefza-I' ecotype was more effective than cultivar 'Marsaoui'.

The extensive applications of Cynomorium species and their rich bioactive secondary metabolites have inspired many pharmacological investigations. Previous research has been conducted to examine the biological activities and numerous interesting pharmaceutical activities have been reported. However, the antitumor activities of these species are unclear. To understand the potential anticancer activity, we screened Cynomorium coccineum and Cynomorium songaricum using three different extracts of each species. In this study, the selected extracts were evaluated for their ability to decrease survival rates of five different cancer cell lines. We compared the cytotoxicity of the three different extracts to the anticancer drug vinblastine and one of the most well-known medicinal mushrooms Amaurederma rude . We found that the water and alcohol extracts of C. coccineum at the very low concentrations possessed very high capacity in decreasing the cancer cells viability with a potential inhibition of tumorigenesis. Based on these primitive data, we subsequently tested the ethanol and the water extracts of C. coccineum , respectively in in vitro and in vivo assays. Cell cycle progression and induction of programmed cell death were investigated at both biological and molecular levels to understand the mechanism of the antitumor inhibitory action of the C. coccineum . The in vitro experiments showed that the treated cancer cells formed fewer and smaller colonies than the untreated cells. Cell cycle progression was inhibited, and the ethanol extract of C. coccineum at a low concentration induced accumulation of cells in the G1 phase. We also found that the C. coccineum 's extracts suppressed viability of two murine cancer cell lines. In the in vivo experiments, we injected mice with murine cancer cell line B16, followed by peritoneal injection of the water extract. The treatment prolonged mouse survival significantly. The tumors grew at a slower rate than the control. Down-regulation of c-myc expression appeared to be associated with these effects. Further investigation showed that treatment with C. coccineum induced the overexpression of the tumor suppressor Foxo3 and other molecules involved in inducing autophagy. These results showed that the C. coccineum extract exerts its antiproliferative activity through the induction of cell death pathway. Thus, the Cynomorium plants appear to be a promising source of new antineoplastic compounds.

The aim of this study was to appraise the response of a multi-marker approach in fish species, Gobius niger and Zosterisessor ophiocephalus, in a polluted lagoon (Bizerte lagoon: MB and ML sites) and in a reference site (Ghar-El-Melh lagoon entrance) by the analysis of physiological indexes, liver histopathology and some biochemical biomarkers. The results showed liver hypertrophy in fish collected from Bizerte lagoon as well as many non-specific lesions, unlike the reference site. All Bizerte lagoon sites had the same prevalence of histopathological lesions, but the mean intensity (MI) of parasites seemed to be more sensible as an indicator of pollution levels. Indeed, parasite MI was more important in MB site that has a higher pollution level. Also, biochemical biomarkers showed an induction in Bizerte lagoon sites with some differences within sites and species. The impact of the continuous release of pollution on the biomarker's response is discussed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: This study aims to investigate whether valproic acid (VPA) anticonvulsant activity varied according to circadian dosing-time in mice., Methods: VPA was administered to mice at four circadian stages (1, 7, 13 and 19h after light onset, (HALO)). The controls received a saline injection followed by a s.c. injection of pentylenetetrazol (PTZ) 30min later. In pretreated animals, VPA was administered 30min before PTZ administration., Results: The results obtained showed that VPA-induced anticonvulsant activity depends on circadian dosing-time in mice. VPA has significantly increased the latency of the first clonic seizure at all circadian stages. This increase varied depending on the time of VPA pre-treatment, the highest and the lowest increases were recorded respectively at 7 and 19 HALO. The Cosinor analysis has also validated a circadian rhythm of this increase. The intensity of seizures in pretreated mice varied significantly according to circadian stage. The highest seizure intensity was recorded at 19 HALO. A circadian rhythm of the seizure intensity in VPA pretreated mice was detected, with an acrophase located at the middle of the dark span (Ø=18.09 HALO±2.27h)., Conclusion: The present findings provide evidence for a pronounced anticonvulsant effect of VPA when administered in the 2nd middle of the light-rest span in mice. These results might probably be due to the circadian variation of VPA pharmacokinetic since our previous studies showed that the optimal tolerance corresponded to the middle of the rest span, the time which induces the highest total plasma clearance., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to evaluate the analgesic and the anti-inflammatory activity of Opuntia microdasys at post flowering stage, F3 (OMF3) in rat and, in other hand, its antigenotoxic effects by the Allium cepa test., Methods: OMF3 extracts were screened for activity of analgesic and anti-inflammatory using, respectively, the acetic acid writhing test in mice and the carrageenan-induced paw oedema assay in rats. The antigenotoxic has been evaluated by A. cepa test., Key Findings: OMF3 extracts showed a higher analgesic and anti-inflammatory activity at 100 mg/kg (72.03% and 70.11%) as determined by the tests of acetic acid-induced writhing and carrageenan-induced oedema, respectively. Furthermore, the OMF3 aqueous extracts have a preventive antimutagenic potential, at lower concentration (EC 50 ≈ 60 μg/ml), against H 2 O 2 -mediated DNA damage in A. cepa root meristem cells with an efficient restoration of the mitotic index in comparison with controls., Conclusions: Based on this study, the flower of O. microdasys at post flowering stage may be use as an analgesic, anti-inflammatory and antimutagenic agents., (© 2017 Royal Pharmaceutical Society.)

This study investigates whether the toxicity in kidneys as well as oxidative stress varied according to the dosing time of an immunosuppressive agent "mycophenolate mofetil (MMF)" in Wistar Rat. 300mg/kg of MMF was injected by intraperitonal at four different circadian stages (1, 7, 13 and 19h after light onset, HALO). Rats were sacrificed after 3days, and the kidneys were removed for determination of oxidative stress and histological analysis. Biochemical variable (creatinine, urea) was performed. Statistical analysis showed that MMF administration at 7 HALO produced a renal toxicity assessed by the significant increase in both blood creatinine and urea and antioxidant activity assessed by malondialdehyde and protein carbonyl levels indicating an induction of lipid peroxidation in oxidative damage. Whereas, at this time MMF induced a decrease the enzyme activities of renal catalase and superoxide dismutase, with a renal histopathology alterations (glomerular atrophy and lesions within proximal tubules). However, when MMF was injected in the middle of the dark-activity phase it produced a very mild renal toxicity and low oxidative stress. The obtained data indicate that the maximum of renal toxicity is observed when MMF was injected in the middle of the light- rest span in rats., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the effects of ethanol-water (80:20) extract of Marrubium vulgare (M. vulgare) on the hematological parameters, macroscopic and histological aspects of the uterus and fetus in non-pregnant and pregnant rats., Methods: Female rats were divided into 4 equal groups (n = 9), group N (normal rats) and group G (pregnant rats) considered as control groups, group NE (normal rats treated with the ethanol-water (80:20, v/v) extract of M. vulgare) and group GE (pregnant rats treated with the extract). The ethanol-water (80:20) plant extract was administered in a single daily dose 1 g/kg at the morning, during 19 d. On the 19 day of the experiment, animals were sacrificed, the uterus and fetuses were removed for the morphological and histological studies and the blood was collected in EDTA tubes for the measurement of hematological parameters with the use of an automate 'HORIBA ABX Micros 60 Hematology Analyzer'., Results: Our results showed, in group NE and GE, a significant decrease on hematological parameters: red blood cells (NE: 18.6%; GE: 38.4%), hematocrit (NE: 13.8%; GE: 20.4%), hemoglobin (NE: 12.1%; GE: 8.3%) and mean corpuscular volume (NE: 6.4%; GE: 2%) with P more less a 0.05. Indeed, the extract of M. vulgare caused a significant decrease on the mean implantations of fetuses (82.5%, P < 0.001) and their size (47.2%, P < 0.01). As for the macroscopic and histological appearance of uterus, our data showed no change in normal treated rats. In contrast, the treated pregnant rats showed a severe histological change characterized by the existence of location of stopped gestation. Furthermore, it was also found in the uterus of these rat lyses placental and embryo tissue., Conclusions: All these results support the hypothesis of an abortifacient effect of M. vulgare., (Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Injury by the sting of Lesser weever fish (Trachinus vipera) may lead to severe pain, edema or tissue necrosis. Cellular effects of the venom are still incompletely understood. Previous observations revealed that purified Lesser weever fish venom (LWFV) induces suicidal death of erythrocytes and HCT116 human colon carcinoma cells. The present study addressed the effect of the venom on colon carcinoma cell toxicity, shape and migration both in p53+/+ and/or p53-/- conditions., Methods: Cells were exposed to medium without or with 500 µg/ ml LWFV. Cell shape, cell area and circularity were visualized and quantified by fluorescence microscopy. Cell volume, granularity and cells toxicity were assessed via the apoptotic parameters dissipation of mitochondrial inner transmembrane potential, phosphatidylserine surface exposure and cell membrane permeabilization were measured utilizing flow cytometry. Cell migration was evaluated using wound healing assay and two-dimensional migration assay., Results: LWFV treatment was followed by a marked change of cell shape and size, significant decrease of cell area and circularity, significant impairment of cell migration, as well as induction of apoptosis after long exposition., Conclusions: LWFV exposure leads to cell shrinkage, increased granularity, apoptosis and impairment of cell migration, effects presumably contributing to LWFV-induced tissue injury., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Accidents caused by the sting of Trachinus vipera (known as Lesser weever fish) are relatively common in shallow waters of the Mediterranean. Symptoms after the sting vary from severe pain to edema or even tissue necrosis in some cases. Here we show that purified Lesser weever fish venom induces eryptosis, the suicidal erythrocyte death, and apoptosis of human colon carcinoma cells. The venom leads to erythrocyte shrinkage, phosphatidylserine translocation and increased intracellular Ca 2+ , events typical for eryptosis. According to mitochondrial staining cancer cells dyed after the activation of the intrinsic apoptotic pathway. Trachinus vipera venom further causes cell cycle arrest.

Introduction: This study is designed to investigate whether the pharmacokinetics of the antituberculous agent isoniazid (INH) varied according to the circadian dosing-time., Methods: A total of 168 male mice aged 10 weeks and synchronized for 3 weeks to 12h light and 12h dark were used. A single INH (100mg/kg) dose was administered by intraperitonal (i.p.) route at either of the four different circadian stages (1, 7, 13 and 19h after light onset, HALO). At each circadian stage, blood samples were withdrawn at 0, 0.1, 0.2, 0.4, 1, 1.3, 2, 2.5, 4, 5, 6.3, 8, 24 and 48h following drug injection. The pharmacokinetics parameters (AUC 0-∞ , Ke, C max , T 1/2, Cl T and V d ) were calculated for each circadian-time., Results: There were relevant differences in C max between the four circadian groups (p<0.005), maximum and minimum C max were obtained when INH was injected at 1 HALO (490mgL -1 ) and at 7 HALO (270mgL -1 ) respectively. AUC 0-∞ also varied significantly according to the circadian-time of injection (2093mgL -1 h -1 at 1 HALO vs 759mgL -1 h -1 at 7 HALO) (p<0.05). The highest and lowest mean values of plasma clearance (Cl) were observed at 7 HALO (0.22Lh -1 kg -1 ) and 1 HALO (0.13Lh -1 kg -1 ) respectively (p<0.05). The Cosinor analysis showed a circadian rhythm in different pharmacokinetic parameters. C max and AUC 0-∞ have a significant circadian rhythm with an acrophase located at 2.64 HALO±0.21h (the beginning of the rest span) (p<0.001), whereas Cl T and V d showed a significant circadian rhythm with an acrophase located respectively at 7.4 HALO and at 8.66 HALO (the second half of the rest span) (p<0.001)., Conclusion: Plasma INH chronopharmacokinetics might be involved in the mechanism of circadian variation of toxicity since the time of optimal tolerance to INH corresponds to that of the lowest C max and AUC 0-∞ and the highest Cl T occured when this drug injected in the second half of light-rest phase (7 HALO)., (Copyright © 2016. Published by Elsevier Masson SAS.)

In the present study, the potential effect anti tumor and the chemical composition of different fractions of Gokshur was evaluated. Commonly known as puncture vine, it has been used for a long time in both the Indian and traditional Chinese medicine. It is popularly used as a remedy for fertility disorder in Ayurveda. Samples were collected during June-September 2014 in the Cap Bon (north east of the northern Tunisia). Different organs were separated and extracted by sequential process to compare and investigate their potential anti-tumor effect. For the first time, we report the antiproliferatif effect of leaves n-butannolic fraction against cancer cell lines. The better anti-tumor fraction (94.76±1.52%) has been detected and performed by RP-HPLC has shown a great peak area (5578.21Mau). Novel designed natural derivatives from Gokshur, a cyclotrisiloxane, major compound identified by GC-MS., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This study aims at evaluating both the influence of natural and some anthropogenic pressures on spatio-temporal variations on biomarker responses in sedentary benthic fish Gobius niger. For this purpose, variability of biotransformation enzymes and oxidative stress parameters response were studied in six stations from Bizerta lagoon as well as a reference station located in Ghar El Melh lagoon. Biomarker responses were shown to vary according to both physico-chemical parameters and anthropogenic pressures, but no influence of sex was reported. Based on multivariate analyses, the responses of biomarkers, obtained after covariate analysis in order to weigh the effect of physico-chemical parameters, allowed us to discriminate all stations, with a good classification rate for those that are highly contaminated. Altogether, this study shows the usefulness of G. niger as a sentinel species and stresses the necessity of integrating natural variables for data interpretation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

3-Aminopropyltrimethoxysilane (APTMS) was used as ligand to prepare ZnO@APTMS, Cu(2+)-doped ZnO (ZnO:Cu@APTMS) and ZnO quantum dots (QDs) with chemisorbed Cu(2+) ions at their surface (ZnO@APTMS/Cu). The dots have a diameter of ca. 5 nm and their crystalline and phase purities and composition were established by X-ray diffraction, transmission electron microscopy, UV-visible and fluorescence spectroscopies and by X-ray photoelectron spectroscopy. The effect of Cu(2+) location on the ability of the QDs to generate reactive oxygen species (ROS) under light irradiation was investigated. Results obtained demonstrate that all dots are able to produce ROS (OH, O2(-), H2O2 and (1)O2) and that ZnO@APTMS/Cu QDs generate more OH and O2(-) radicals and H2O2 than ZnO@APTMS and ZnO:Cu@APTMS QDs probably via mechanisms associating photo-induced charge carriers and Fenton reactions. In cytotoxicity experiments conducted in the dark or under light exposure, ZnO@APTMS/Cu QDs appeared slightly more deleterious to Escherichia coli cells than the two other QDs, therefore pointing out the importance of the presence of Cu(2+) ions at the periphery of the nanocrystals. On the other hand, with the lack of photo-induced toxicity, it can be inferred that ROS production cannot explain the cytotoxicity associated to the QDs. Our study demonstrates that both the production of ROS from ZnO QDs and their toxicity may be enhanced by chemisorbed Cu(2+) ions, which could be useful for medical or photocatalytic applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

There is controversy about the anti- or pro-oxidative effects of the nitric oxide (NO)-donor sodium nitroprusside (SNP). Hence, the activity of the antioxidant enzyme catalase (CAT) and the status of malondialdehyde (MDA) were investigated after a 2.5 mg/kg dose of SNP had been i.p. administered to different and comparable groups of mice (n = 48). The drug was administered at two different circadian times (1 and 13 h after light onset [HALO]). There were, irrespectively of sampling time, no significant differences in the means of CAT activity and MDA status between control and SNP-treated groups, no matter the treatment time. However, CAT activity was significantly (Student's t-test, p < 0.001) increased 1 h following SNP administration at 1 HALO, whereas the significant (p < 0.001) increase in the enzyme activity was found only 3 h after injection at 13 HALO. The drug dosing either at 1 or 13 HALO resulted in no significant differences of MDA status between control and treated groups regardless to the sampling time. Two-way analysis of variance (ANOVA) detected a significant (F0.05(7,88)= 5.3; p < 0.0006) interaction between sampling time and treatment in mice injected at 1 HALO, suggesting the influence of treatment on sampling-time-related changes in CAT activity. However, ANOVA validated no interaction between the two factors in mice treated at 13 HALO, illustrating that the sampling-time differences in enzyme activity were greater. Furthermore, two-way ANOVA revealed no interaction in the variation of MDA status in animals treated either at 1 or 13 HALO. This study indicates that SNP significantly affected the anti-oxidant system.

Immunosuppressive drugs such as Mycophenolate Mofetil (MMF) are used to suppress the immune system activity in transplant patients and reduce the risk of organ rejection. The present study investigates whether the potential cytotoxicity and genotoxicity varied according to MMF dosing-time in Wistar Rat. A potentially toxic MMF dose (300 mg/kg) was acutely administered by the i.p. route in rats at four different circadian stages (1, 7, 13 and 19 hours after light onset, HALO). Rats were sacrificed 3 days following injection, blood and bone marrow were removed for determination of cytotoxicity and genotoxicity analysis. The genotoxic effect of this pro-drug was investigated using the comet assay and the micronucleus test. Hematological changes were also evaluated according to circadian dosing time. MMF treatment induced a significant decrease at 7 HALO in red blood cells, in the hemoglobin rate and in white blood cells. These parameters followed a circadian rhythm in controls or in treated rats with an acrophase located at the end of the light-rest phase. A significant, thrombocytopenia was observed according to MMF circadian dosing time. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, poikilocytotic in red cells and hypersegmented neutrophil nuclei were observed with MMF treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow; the comet assay showed significant DNA damage. This damage varied according to circadian MMF dosing time. The injection of MMF in the middle of the dark-activity phase produced a very mild hematological toxicity and low genotoxicity. Conversely, it induced maximum hematological toxicity and genotoxicity when the administration occurred in the middle of the light-rest phase, which is physiologically analogous to the end of the activity of the diurnal phase in human patients.

Cereus peruvianus (Peruvian apple cactus) is a large erect and thorny succulent cactus characterized by column-like (cereus [L]: column), that is, candle-shaped, appendages. For three successive years (1100 days), between early April and late November, we studied the flowering patterns of eight cacti growing in public gardens and rural areas of north and central Tunisia, far from nighttime artificial illumination, in relation to natural environmental light, temperature, relative humidity and precipitation parameters. Flower blooming was assessed nightly between 23:00 h and until at least 02:00 h, and additionally around-the-clock at ~1 h intervals for 30 consecutive days during the late summer of each year of study to quantify both nyctohemeral (day-night) and lunar patterns. During the summer months of prolonged daytime photoperiod, flower blooming of C. peruvianus exhibited predictable-in-time variation as "waves" with average period of 29.5 days synchronized by the light of the full moon. The large-sized flower (~16 cm diameter) opens almost exclusively at night, between sunset and sunrise, as a 24 h rhythm during a specific 3-4-day span of the lunar cycle (full moon), with a strong correlation between moon phase and number and proportion of flowers in bloom (ranging from r = +0.59 to +0.91). Black, blue and red cotton sheets were used to filter specific spectral bands of nighttime moonlight from illuminating randomly selected plant appendages as a means to test the hypothesis of a "gating" 24 h rhythm phenomenon of photoreceptors at the bud level. Relative to control conditions (no light filtering), black sheet covering inhibited flower bud induction by 87.5%, red sheet covering by 46.6% and blue sheet covering by 34%, and the respective inhibiting effects on number of flowers in bloom were essentially 100%, ~81% and ~44%. C. peruvianus is a unique example of a terrestrial plant that exhibits a circadian flowering rhythm (peak ~00:00 h) "gated" by 24 h, lunar 29.5-day (bright light of full moon) and annual 365.25-day (prolonged summertime day length) environmental photoperiod cycles.