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We compute a lower bound of Billingsley–Hausdorff dimension, defined by Gibbs measure, of the level set related to Birkhoff average in the countable symbolic space $\mathbb{N}^{\mathbb{N}}$.

The antiviral activities of extracts from Daucus maritimus seeds were investigated against the reverse transcriptase of human immunodeficiency virus (HIV) type 1 and a panel of RNA-dependent RNA polymerases of dengue virus, West Nile virus (WNV) and hepatitis C virus (HCV). The extracts showed moderate to potent inhibition rates against the four viral polymerases. The ethyl acetate extract exhibited a potent inhibitory effect against WNV's RdRp, with an IC50 value of 8 µg mL−1. The F2 fraction exhibited potent inhibitory activity against WNV and HCV's RdRps, with IC50 values 1 and 5 µg mL−1, respectively. The P2 fraction also showed potent inhibitory effects on WNV and HCV's RdRps, with IC50 values 2.7 and 4 µg mL−1, respectively. The results suggest that these extracts are candidates for the development of new anti-WNV RpDp and anti-HCV RpDp agents. [ABSTRACT FROM AUTHOR]

This appendix gives a lower bound of the Billingsley-Hausdorff dimension of a level set related to Birkhoff average in the “non-compact” symbolic space $\mathbb{N}^{\mathbb{N}}$, defined by Gibbs measure.

Addressing a single target is the frequent development of drug resistance followed by cancer relapse and treatment failure. Therefore, assessment of simultaneous expression of target molecules is essential to choose the optimal combination therapy for each colorectal cancer patient. This study aims to evaluate the immunohistochemical expression of HIF1α, HER2 and VEGF and to clarify their clinical significance as prognostic factors and predictive markers of FOLFOX (combination chemotherapy inclusive of Leucovorin calcium, Fluorouracil and Oxaliplatin response). Marker expression was retrospectively evaluated by immunohistochemistry in 111 patients with colorectal adenocarcinomas from south Tunisia, followed by statistical analysis. The immunohistochemical staining revealed that 45 %, 80.2 %, 86.5 % and 25.5 % of specimen were positive for nuclear, cytoplasmic HIF1α expression, VEGF and HER2 respectively. Nuclear HIF1α and VEGF were associated with worst prognosis while cytoplasmic HIF1α and HER2 were correlated with favourable prognosis. Multivariate analysis confirms the association between nuclear HIF1α, distant metastasis, relapse, FOLFOX response and 5 years overall survival. HIF1α positivity and HER2 negativity were significantly associated to short survival. Combined immunoprofiles HIF1α+/VEGF+, HIF1α+/HER2-, HIF1α+/VEGF+/HER2- were associated to distant metastasis, cancer relapse and short survival. Interestingly, our findings confirmed that patients bearing a HIF1α positive tumor were significantly more resistant to FOLFOX compared to negative ones (p = 0.002, p ≤ 0.001). Positive expression of HIF1α and VEGF, or decreased expression of HER2 was each associated with poor prognosis and short overall survival. In summary, we found that expression of nuclear HIF1α, alone or combined with VEGF and HER2 serves as a predictive marker of poor prognosis and FOLFOX response in colorectal cancer from south Tunisia., Competing Interests: Declaration of competing interest The author (s) declared no potential conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as well as its expression. Methylation profiles of ERCC1 and MGMT were tested by methylation-specific PCR. A polymorphism of ERCC1 was studied using PCR-RFLP and its expression was examined by immunohistochemistry. ERCC1 was methylated in 44.6% of colorectal adenocarcinoma while MGMT was methylated in 69% of cases. MGMT methylation was strongly associated with lymph node metastasis, lymph invasion, venous invasion, perineural invasion, distant metastasis and relapse. Patients with methylation of both genes were more likely to have a poor prognosis and display chemoresistance. IHC analysis revealed that ERCC1 staining was noted in 52.8% of colorectal adenocarcinoma and inversely related to distant metastasis and cancer recurrence. Kaplan Meier analysis revealed that the worst overall survival was significantly associated with ERCC1 and MGMT methylation while decreased ERCC1 expression and T/T genotype exhibited the best overall survival. The methylation of MGMT, alone or combined with ERCC1, is predictive for poor prognosis, short overall survival and chemotherapy response in colorectal cancer.

Wild Vitex agnus-castus (VAC) is a Mediterranean plant that is rich in bioactive metabolites. This study aimed to validate, for the first time, the beneficial use of VAC fruits and fruit decoctions (VFDs) through in vitro and in vivo trials. Forty-one volatile components were detected in VAC fruits, with 1,8-cineole (30.3%) comprising the majority. The antioxidant activity of VFD was measured by using different in vitro methods (EC 50 of 0.16 mg/mL by β-carotene bleaching inhibition assay) and by measuring the DNA protection power. Using the disc diffusion assay, the antimicrobial activity of VFD was evaluated, and it exhibited a noticeable anticandidal activity. VFD did not cause any toxicity or mortality in rats treated with doses > 200 mg/kg. Using the acetic acid writhing test, the antinociceptive activity of VFD was measured. Our results showed that VFD at 200 mg/kg exhibited a higher analgesic activity (81.68%) than acetylsalicylic acid used as a positive control (74.35%). Its gastroprotective ability was assessed by HCl/ethanol-induced gastric lesions, which were remarkably inhibited (84.62%) by intraperitoneal administration of VFD. This work helps to validate the popular use of VAC to treat nociceptive, inflammatory, and gastric disorders and encourages researchers to further investigate the identification of pharmacological compounds from this species.

Colorectal cancer (CRC) is a common health issue worldwide with an extremely low survival rate after relapse. This study aims to evaluate the immunohistochemical expression of p53, E-cadherin, Bcl-2 and Bcl-xL and find a potential correlation between these markers, clinicopathological factors and overall survival of colorectal cancer patients. Marker expression was immunohistochemically determined in 105 patients with colorectal adenocarcinoma from southern Tunisia, followed by statistical analysis. Positivity rate of nuclear p53, membranous E-cadherin and cytoplasmic Bcl-2 - Bcl-xL was 85.71%, 76.47%, 59.8%, and 85.71% respectively. Spearman correlation showed that p53 was significantly and positively related to E-cadherin, Bcl-2, Bcl-xL and distant metastasis. A positive significant correlation between E-cadherin and anti-apoptotic proteins was also seen. Membranous E-cadherin expression was significantly and negatively associated to poor prognosis factors including lymph node metastasis, lymph invasion, venous invasion and distant metastasis. Bcl-2 expression was significantly correlated to distant metastasis. Multivariate analysis showed a significant association between dependent variable E-cadherin and covariates including differentiation, lymph invasion, venous invasion, distant metastasis, Bcl-2 and Bcl-xL. Poor 3-years OS and 5-years OS were significantly related to p53, Bcl-2 expression and E-cadherin loss. Positive E-cadherin combined with negative p53 and Bcl-2 as well as double-positive for E-cadherin and Bcl-xL were associated to best overall survival. Although each protein can be an independent prognostic factor, Simultaneous E-cadherin, p53, Bcl-2, Bcl-xL expression could be a crucial prognostic and overall survival marker to CRC patients. Multivariate analysis confirmed a positive correlation between membranous E-cadherin loss and colorectal cancer severity.

Recently, β-carotene has gained tremendous importance as a bioactive molecule due to the growing awareness of the harmful effects of synthetic products. β-carotene is a high-value natural pigment that has the highest demand in the global carotenoid market owing to its proven antioxidant properties relevant for several diseases. To date, Dunaliella salina is the most important producer of natural β-carotene and is the subject of important industrial efforts. However, the extraction of β-carotene remains challenging since all the proposed techniques present a risk of product contamination or loss of quality due to solvent residuals and low yields. The purpose of this study was to set up a green, ecological, and innovative process of extraction of the two major β-carotene isomers from the halophilic microalgae Dunaliella salina . Based on molecular modeling, docking, and drug design, we conceived and synthesized two chimeric peptides (PP2, PP3) targeting specifically the two major isomers: all-trans or 9-cis β-carotene. The experimental protocol used in this study demonstrated the ability and the efficacy of those two peptides to cross the cell membrane and bind with high affinity to β-carotene isomers and exclude them toward the extracellular medium while preserving the integrity of living cells. Interestingly, the tested peptides (PP2, PP3) exhibit significant β-carotene extraction yields 58% and 34%, respectively, from the total of the β-carotene in microalgae cells. In addition to its simplicity, this process is fast, independent of the source of the β-carotene, and selective. These results would allow us to set up a green, ecological, and very profitable process of extraction from microalgae containing high amounts of β-carotene. Our innovative approach is highly promising for the extraction of Dunaliella salina biomass on an industrial scale., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

The production of extra virgin olive oil (EVOO) flavored with diverse spices, herbs, fruits, and vegetables or natural aromas is believed to provide advantageous properties considering either the high nutritional value or biological activity in addition to the flavoring and industrial aspects. The biological activities including antioxidant and antimicrobial properties of Tunisian EVOO obtained from "Chemlali" variety and mixed with chili pepper were investigated. Molecular analyses, including the detection of twelve olive-infecting viruses and Pseudomonas savastanoi pv savastanoi, were performed to ensure that the samples were obtained from healthy olive trees and EVOO quality was not affected. Quality parameters like free acidity, peroxide number, oxidative stability, and specific absorption at K232 nm and K270 nm were also investigated and no significant variation was revealed. The content of minor compounds such as chlorophylls, carotenoids, and total phenols showed minor changes. However, the profiles of the volatile compounds showed remarkable differences, which appeared to be the main factor for the observed variability in consumer acceptance. The results showed for the first time high quantities of polyphenols and ortho-diphenols. Four colorimetric methods were used for the determination of the antioxidant activity, namely DPPH, ABTS, FRAP, and β-carotene test. Compared to the control, a higher level of antioxidant activity was observed for the flavored EVOO. Furthermore, significant results were obtained in the antimicrobial tests. The quality parameters of the mixture showed no alteration compared to the control. Finally, all the measurements and the chemical characterization gave a scientific basis for food technology innovation of new food products., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

With an estimated 1 billion people affected across the globe, influenza is one of the most serious health concerns worldwide. Therapeutic treatments have encompassed a number of key functional viral proteins, mainly focused on the M2 proton channel and neuraminidase. This review highlights the efforts spent in targeting the M2 proton channel, which mediates the proton transport toward the interior of the viral particle as a preliminary step leading to the release of the fusion peptide in hemagglutinin and the fusion of the viral and endosomal membranes. Besides the structural and mechanistic aspects of the M2 proton channel, attention is paid to the challenges posed by the development of efficient small molecule inhibitors and the evolution toward novel ligands and scaffolds motivated by the emergence of resistant strains., Competing Interests: The 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 Aledavood, Selmi, Estarellas, Masetti and Luque.)

Pergularia tomentosa L. (P. tomentosa) has been largely used in Tunisian folk medicine as remedies against skin diseases, asthma, and bronchitis. The main objectives of this study were to identify phytochemical compounds that have antioxidant and antimicrobial properties from the stem, leaves, and fruit crude methanolic extracts of P. tomentosa, and to search for tyrosyl-tRNA synthetase (TyrRS), topoisomerase type IIA, and Candidapepsin-1 (SAP1) enzyme inhibitors through molecular docking study. Phytochemical quantification revealed that fruit and leaves extracts displayed the highest total flavonoids (582 mg QE/g Ex; 219 mg QE/g Ex) and tannins content (375 mg TAE/g Ex; 216 mg TAE/g Ex), also exhibiting significant scavenging activity to decrease free radicals for ABTS, DPPH, β-carotene, and FRAP assay with IC 50 values (> 1 mg/mL). Additionally, promising antimicrobial activities towards different organs have been observed against several bacteria and Candida strains. From the liquid chromatography-mass spectrometry (LC-MS) analysis, five polyphenolic compounds, namely digitoxigenin, digitonin glycoside and calactina in the leaves, kaempferol in the fruit, and calotropagenin in the stems, were identified. They were also analyzed for their drug likeliness, based on computational methods. Molecular docking study affirmed that the binding affinity of calactin and actodigin to the active site of TyrRS, topoisomerase type IIA, and SAP1 target virulence proteins was the highest among the examined dominant compounds. Therefore, this study indicated that P. tomentosa methanolic extracts displayed great potential to become a potent antimicrobial agent and might be a promising source for therapeutic and nutritional functions. These phytocompounds could be further promoted as a candidate for drug discovery and development.

Background: Despite synchronization to respiration, respiration-navigated (RN) 3D turbo-spin-echo MRCP is limited by susceptibility to motion artifacts. The aim of this study was to assess the quality of pancreaticobiliary duct visualization of a non-RN MRCP alternative based on balanced steady-state free precession imaging (BSSFP) with overlapping slices compared with RN-MRCP., Methods: This is a retrospective study on 50 patients without pancreaticobiliary duct disease receiving MRCP at 1.5 T. We performed an intraindividual comparison of coronal RN-MRCP with combined coronal and transverse BSSFP-MRCP. Image quality was scored by 3 readers for 6 pancreaticobiliary duct segments (3 pancreatic, 3 biliary) using a 6-point scale. A segment score of 3 or lower as assessed by at least 2 of 3 readers was defined as insufficient segment visualization. Nonparametric tests and interrater reliability testing were used for statistical analysis., Results: Overall duct visualization averaged over all readers was scored with 4.5 ± 1.1 for RN-MRCP (pancreatic, 4.1 ± 0.5; biliary, 5.0 ± 0.4) and 4.9 ± 0.9 for combined coronal and transverse BSSFP-MRCP (pancreatic, 4.6 ± 0.6; biliary, 5.1 ± 0.6), respectively (p < 0.001). The number of segments visualized insufficiently was 81/300 for RN-MRCP and 43/300 for BSSFP-MRCP (p < 0.001). Segments visualized insufficiently only in RN-MRCP had a mean score of 4.4 ± 0.8 in BSSFP-MRCP. Overall interrater agreement on superiority of BSSFP-MRCP segment scores over corresponding RN-MRCP was 0.70. Mean acquisition time was 98% longer for RN-MRCP (198.0 ± 98.7 s) than for combined coronal and transverse BSSFP-MRCP (100.2 ± 0.4 s)., Conclusions: Non-RN BSSFP-MRCP with overlapping slices is a fast alternative to RN-MRCP, frequently providing sufficient duct visualization when RN-MRCP fails.

The study investigated the human cytomegalovirus (HCMV) and human papillomavirus (HPV) in gliomas. A retrospective study was conducted on 112 samples. HCMV was investigated by PCR, in situ hybridization (ISH) and immunohistochemistry. HPV was tested by PCR and DNA ISH. HCMV was identified in 60 gliomas, including 55 GBM. However, RNA ISH and immunohistochemistry failed to detect HCMV positivity. HPV was identified in 44 GBM. No significant relationship was identified between HCMV and HPV and tumour characteristics ( p  > 0.05). Our findings support the HCMV and HPV presence in gliomas. Further assays are required to more explore the potential efficient antiviral management.

The gliomagenesis remains not fully established and their etiological factors still remain obscure. Polyomaviruses were detected and involved in several human tumors. Their potential implication in gliomas has been not yet surveyed in Africa and Arab World. Herein, we investigated the prevalence of six polyomaviruses (SV40, JCPyV, BKPyV, MCPyV, KIPyV, and WUPyV) in 112 gliomas from Tunisian patients. The DNA sequences of polyomaviruses were examined by PCR assays. Viral infection was confirmed by DNA in situ hybridization (ISH) and/or immunohistochemistry (IHC). The relationships between polyomavirus infection and tumor features were evaluated. Specific SV40 Tag, viral regulatory, and VP1 regions were identified in 12 GBM (10.7%). DNA ISH targeting the whole SV40 genome and SV40 Tag IHC confirmed the PCR findings. Five gliomas yielded JCPyV positivity by PCR and DNA ISH (2.7%). However, no BKPyV, KIPyV, and WUPyV DNA sequences were identified in all samples. MCPyV DNA was identified in 30 gliomas (26.8%). For GBM samples, MCPyV was significantly related to patient age (p = 0.037), tumor recurrence (p = 0.024), and SV40 (p = 0.045) infection. No further significant association was identified with the remaining tumor features (p > 0.05) and patient survival (Log Rank, p > 0.05). Our study indicates the presence of SV40, JCPyV, and MCPyV DNA in Tunisian gliomas. Further investigations are required to more elucidate the potential involvement of polyomaviruses in these destructive malignancies.

Objective: To evaluate the effect of the administration of phytoestrogens on obesity, type 2 diabetes, and liver-kidney toxicity. Methods: Phytoestrogens (phyto(E2)) were administrated to high fructose-fat diet (HFFD). Results: This study showed that administration of phyto(E2) to HFFD-mice inhibited lipase activity by 34%, decreased body weight by 20% and modulated lipid profile, showed a decrease in total-cholesterol (TC) and LDL-cholesterol (LDL-C) rates in the plasma by 59% and 42%, respectively, and increased the HDL-cholesterol (HDL-C) level by 31%. In addition, the administration of phytoestrogens to HFFD-mice exerts an inhibitory effect on α-amylase activity and decreased glucose level by 28% and increase in liver glycogen level by 33%; and ameliorate oral glucose tolerance test. Conclusions: This study demonstrate that phyto(E2) has both a promising potential with regards to the inhibition of intestinal lipase and α-amylase activities, and a valuable hypoglycemic and hypolipidemic function.

The nutritional values, the identification of individual phenolic compounds as well as the functional properties (in vitro acetylcholinesterase (AChE) and pancreatic lipase inhibition) of Tunisian Feijoa sellowiana (O.Berg) leaves were determined by high-performance liquid chromatography coupled with diode array and mass spectrometry detector. Feijoa Sellowiana  leaves Extract (FSLE) were evaluated in the present work. Macronutrient components (proteins, carbohydrates, dietary fiber, lipids, and ashes) of FSLE as well as their fatty acids and mineral content were determined. The individual phenolic composition was characterized by the presence of flavonols (mostly quercetin glycosides), flavan-3-ols (procyanidins and catechins), and phenolic acid derivatives. To understand the possible inhibition mechanism exerted by the extract components, enzyme kinetic studies using derived Lineweaver-Burk (LB) plots and Michaelis-Menten were performed. The obtained results evidenced that FSLE exhibited important AChE inhibitory effect, behaving as a noncompetitive inhibitor. Furthermore, the leaves' extract inhibited irreversibly the pancreatic lipase, with maximum inhibition (70%) achieved at 1 mg/ml. PRACTICAL APPLICATIONS: In many countries of the world, Feijoa Sellowiana leaves are used as an alternative to tea drinks and as a folkloric medicine. Moreover, it is well known that the phytochemical compounds are a practical alternative for the prevention of many chronic diseases such as Alzheimer's and obesity. For this reason, the present study aimed to evaluate the nutritional, individual phenolic compounds, and functional properties of Feijoa Sellowiana leaves to valorize them as a food and pharmaceutical bioactive human source., (© 2019 Wiley Periodicals, Inc.)

The study investigated the pattern of MGMT promoter methylation and the expression of MGMT, P53, EGFR, MDM2 and PTEN proteins in glioblastomas multiforme (GBM) and evaluated their prognostic significance. We carried out a retrospective study of 80 GBM. Expression of MGMT as well as of P53, EGFR, MDM2 and PTEN was investigated by immunohistochemistry. MGMT promoter methylation was investigated by methylation specific-PCR of bisulfite-treated DNA. Twenty-five GBM exhibited MGMT expression. Methylation of MGMT promoter was detected in 35.1% of cases. No significant concordance was reported between MGMT promoter methylation and protein expression (κ=-0.047, p=0.11). MGMT promoter methylation was significantly associated only with PTEN expression (p=0.001): no other significant association was identified with clinical parameters as well as with expression of P53, EGFR and MDM2 (p >0.05). Tumor recurrence was significantly associated with unmethylated MGMT promoter (p=0.01) but not with MGMT expression (p=0.51). Recurrence-free survival (RFS) was significantly better among patients with methylated MGMT promoter (log rank, p <0.0001) and PTEN expression (log rank, p=0.025) but not with MGMT expression (log rank, p=0.308). As well, using univariate analysis, MGMT promoter methylation (p=0.001) and PTEN expression (p=0.044) were significantly associated with RFS. In multivariate analysis, only MGMT promoter methylation was significantly associated with RFS (p=0.003). Together, our findings support that MGMT protein expression doesn't reflect the MGMT promoter methylation status. Furthermore, MGMT promoter methylation remains a useful prognostic marker in Tunisian patients with GBM. PTEN expression could be a potential prognostic marker of this tumor.

A series of enantiopure isoxazolidines (3a-c) were synthesized by 1,3-dipolar cycloaddition between a (-)-menthone-derived nitrone and various terminal alkenes. The screened compounds were evaluated for their antioxidant activity by two in vitro antioxidant assays, including β-carotene/linoleic acid bleaching, and inhibition of lipid peroxidation (thiobarbituric acid reactive species, TBARS). The results revealed that compound 3b (EC 50  = 0.55 ± 0.09 mM) was the most potent antioxidant as compared to the standard drug (EC 50  = 2.73 ± 0.07 mM) using the TBARS assay. Furthermore, the antimicrobial activity was assessed using disc diffusion and microdilution methods. Among the synthesized compounds, 3c was found to be the most potent antimicrobial agent as compared to the standard drug. Subsequently, the acute toxicity study has also been carried out for the newly synthesized compounds and the experimental studies revealed that all compounds were safe up to 500 mg/kg and no death of animals were recorded. The cytotoxicity of these compounds was assessed by the MTT cell proliferation assay against the continuous human cell lines HeLa and compound 3c (GI 50  = 46.2 ± 1.2 μM) appeared to be more active than compound 3a (GI 50  = 200 ± 2.8 μM) and 3b (GI 50  = 1400 ± 7.8 μM). Interestingly, all tested compounds displayed a good α-amylase inhibitory activity in competitive manner with IC 50 values ranging between 23.7 and 64.35 μM when compared to the standard drug acarbose (IC 50  = 282.12 μM). In addition, molecular docking studies were performed to understand the possible binding and the interaction of the most active compounds to the α-amylase pocket.

Background: α-glucosidase is a therapeutic target for diabetes mellitus (DM) and α-glucosidase inhibitors play a vital role in the treatments for the disease. Furthermore, xanthine oxidase (XO) is a key enzyme that catalyzes hypoxanthine and xanthine to uric acid which at high levels can lead to hyperuricemia which is an important cause of gout. Pancreatic lipase (PL) secreted into the duodenum plays a key role in the digestion and absorption of fats. For its importance in lipid digestion, PL represents an attractive target for obesity prevention., Methods: The flowers essential oil of Rhaponticum acaule (L) DC (R. acaule) was characterized using gas chromatography-mass spectrometry (GC-MS). The antioxidant activities of R. acaule essential oil (RaEO) were also determined using 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), reducing power, phosphomolybdenum, and DNA nicking assays. The inhibitory power of RaEO against α-glucosidase, xanthine oxidase and pancreatic lipase was evaluated. Enzyme kinetic studies using Michaelis-Menten and the derived Lineweaver-Burk (LB) plots were performed to understand the possible mechanism of inhibition exercised by the components of this essential oil., Results: The result revealed the presence of 26 compounds (97.4%). The main constituents include germacrene D (49.2%), methyl eugenol (8.3%), (E)-β-ionone (6.2%), β-caryophyllene (5.7%), (E,E)-α-farnesene (4.2%), bicyclogermacrene (4.1%) and (Z)-α-bisabolene (3.7%). The kinetic inhibition study showed that the essential oil demonstrated a strong α-glucosidase inhibiton and it was a mixed inhibitor. On the other hand, our results evidenced that this oil exhibited important xanthine oxidase inhibitory effect, behaving as a non-competitive inhibitor. The essential oil inhibited the turkey pancreatic lipase, with maximum inhibition of 80% achieved at 2 mg/mL. Furthermore, the inhibition of turkey pancreatic lipase by RaEO was an irreversible one., Conclusion: The results revealed that the RaEO is a new promising potential source of antioxidant compounds, endowed with good practical applications for human health.

The emergence of multidrug resistant pathogens threatened the clinical efficacy of many existing antibiotics. This situation has been recognized globally as a serious concern and justifies further research to discover antimicrobial agents from natural origins including plant extracts. The aim of our work was to evaluate the antimicrobial activities of Scabiosa arenaria Forssk. extracts and pure compounds using a bioguided fractionation, and try to explain some traditional use of this genus. The best antimicrobial activity-guided fractionation was obtained by BuOH fractions of flowers, fruits and (stems and leaves) against Escherichia coli, Pseudomonas aeruginosa and Candida albicans with minimum inhibitory concentration (MIC) values from 0.0195 to 5 mg/ml. Escherichia coli was the most affected bug, thus the MIC of fruits BuOH extract showed the best anti-Escherichia coli activity (MIC = 0.0195 mg/ml), followed by the (stems and leaves) and flowers BuOH extracts; MIC = 0.078 and 0.15 mg/ml, respectively. Furthermore, the subfractions obtained from these three mixed fractions showed also an important antimicrobial activity against the three microorganisms, with MIC values between 0.0195 and 0.312 mg/ml. The fractionation of the aerial part BuOH fraction led to the isolation of oleanolic acid (1) and luteolin 7-O-glucopyranoside (2) which are reported here for the first time from S. arenaria. Both compounds showed good antimicrobial activities with MIC values ranging from 170 to 683 μm and 86 to 347 μm, respectively. These results support the use of the Scabiosa genus to inhibit the growth of tested pathogenic bacteria and yeasts which may reduce illnesses associated with their exposure., (© 2016 Wiley-VHCA AG, Zürich.)

Context To date, there are no reports to validate the Tunisian traditional and folklore claims of Eruca vesicaria (L) Cav. subsp. longirostris (Brassicaceae) for the treatment of disease. Objective Investigation of the chemical composition antimicrobial and antioxidant activity of essential oils from Eruca longirostris leaves, stems, roots and fruits. Materials and methods The essential oils of E. longirostris from leaves, stems, roots and fruits were obtained after 4 h of hydrodistillation. Chemical compositions were determined using a combination of GC/FID and GC/MS. The in vitro antimicrobial activity of the volatile constituents of E. longirostris was performed in sterile 96-well microplates against three Gram-positive, four Gram-negative bacteria and one strain as yeast. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values were reported. Furthermore, the antioxidant activity was evaluated by DPPH and ABTS assays. Results The main compound for fruits, stems and roots was the erucin (96.6%, 85.3% and 83.7%, respectively), while β-elemene (35.7%), hexahydrofarnesylacetone (23.9%), (E)-β-damascone (15.4%), erucin (10.6%) and α-longipinene (9.6%) constituted the major compounds in the essential oil of the leaves. The experimental results showed that in all tests, essential oil of fruits showed the better antioxidant activity than the others. On the other hand, the oils of stems, fruits and roots showed significant antimicrobial activity with MIC values ranging from 0.125 to 0.31 mg/mL against Candida species, Gram-positive and Gram-negative bacteria, mainly Salmonella enterica. Conclusions The present results indicate that essential oils of E. longirostris can be used as a source of erucin.

Objectives: This work describes the bioguided fractionation of the flower's ethyl acetate fraction of Scabiosa arenaria Forssk. (Dipsacaceae)., Methods: The identification of the pure compound isolated has been studied by mono-dimensional NMR experiments. The mixture of phenolic compounds was analysed by LC-ESI-MS/MS. The antioxidant activity has been evaluated by the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay., Key Findings: The bioguided fractionation of the flower's ethyl acetate fraction of Scabiosa arenaria led to the isolation of a pure compound: luteolin. The mixture of three phenolic compounds was identified as: 1, 4-O-dicaffeoylquinic acid, apigenin 7-O-glucoside and luteolin-7-O-glucoside. Two of which are reported here for the first time in Scabiosa genus. Luteolin had the highest antioxidant activity with an IC50 value of 0.02 ± 0.007 mg/ml, followed by the three phenolic compounds with an IC50 value of 0.025 ± 0.008 mg/ml., Conclusions: The results of the present work indicate that S. arenaria flower's ethyl acetate extract could be used as natural antioxidant agents in food preservation and human health., (© 2016 Royal Pharmaceutical Society.)

Recent decades have witnessed a sharp increase in the incidence and prevalence of type 2 diabetes mellitus. One antidiabetic therapeutic approach is to reduce gastrointestinal glucose production and absorption through the inhibition of carbohydrate-digesting enzymes such as α-amylase and α-glucosidase. In this study, crude extracts and their corresponding fractions of flowers, fruits, (stems and leaves) and roots of the endemic North African plant Scabiosa arenaria Forssk. were screened for their ability of α-glucosidase inhibition. It was found that the fruits ethyl acetate (EtOAc), the fruits butanolic (n-BuOH) and the flowers ethyl acetate (EtOAc) fractions inhibited α-glucosidase in a non competitive manner with IC50 values of 0.11±0.09, 0.28±0.04 and 0.221±0.01mg/ml, respectively. RP-HPLC analysis indicated that the major components of these active fractions are flavonoid aglycone, cinnamic acid and its derivatives. This result supports the conclusion that the three studied fractions could be a useful natural source for the development of a novel α-glucosidase inhibitory agent against diabetic complications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: To determine the value of real-time tissue elastography (RTE) in pediatric liver diseases in comparison to liver biopsy., Methods: RTE was performed on 34 patients (♀, n = 17; ♂, n = 17; range 0-21 years) with various acute and chronic liver diseases: autoimmune hepatitis (n = 5), liver transplantation (n = 5), Wilson's disease (n = 4), hepatopathy of unknown origin (n = 4), unclear cholestatic hepatitis (n = 2), thalassemia major (n = 2), glycogenosis (n = 2), hereditary fructose intolerance (n = 1), alpha-1-antitrypsin deficiency (n = 1), diabetes mellitus type 1 (n = 1), chronic intestinal pseudo-obstruction (n = 1), primary sclerosing cholangitis (n = 1), hepatitis B (n = 1), cirrhosis of unknown origin (n = 1), drug-induced hepatopathy (n = 1), unexplained transaminase elevation (n = 1), and nonalcoholic steatohepatitis (n = 1). Included children were biopsied. RTE was performed on a control group (n = 30; ♀, n = 15; ♂, n = 15). The mean value of strain (MEAN) in arbitrary units and the ratio of blue color-coded harder tissue (AREA) were calculated based on an elasticity histogram of the selected region of interest in liver parenchyma. They were compared with the histologically defined grade of liver fibrosis., Results: In comparison to the scoring systems, a moderate correlation was observed for MEAN and AREA by excluding the F0 patients [MEAN r = -0.575 to -0.645, AREA r = 0.545-0.607 (p < 0.05)]. Differentiation of the control group and low-grade fibrosis (F1) from high-grade fibrosis (F2-4) was significantly possible (p values <0.001 at 5 % significance level)., Conclusion: RTE parameters enable a possible differentiation of high fibrosis; however, their correlation with fibrosis stage was moderate. RTE seems to be a promising method in liver fibrosis grading in children.

Purpose: We aimed to determine the comparability of real-time tissue elastography (RTE) and transient elastography (TE) in pediatric patients with liver diseases., Materials and Methods: RTE was performed on the Elasticity QA Phantom Model 049 (Computerized Imaging Reference Systems Company Inc., Norfolk, Virginia, USA), which has five areas with different levels of stiffness. RTE measurements of relative stiffness (MEAN [mean value of tissue elasticity], AREA [% of blue color-coded stiffer tissue]) in the phantom were compared with the phantom stiffness specified in kPa (measurement unit of TE). RTE and TE were performed on 147 pediatric patients with various liver diseases. A total of 109 measurements were valid. The participants had following diseases: metabolic liver disease (n=25), cystic fibrosis (n=20), hepatopathy of unknown origin (n=11), autoimmune hepatitis (n=12), Wilson's disease (n=11), and various liver parenchyma alterations (n=30). Correlations between RTE and TE measurements in the patients were calculated. In addition, RTE was performed on a control group (n=30), and the RTE values between the patient and control groups were compared., Results: The RTE parameters showed good correlation in the phantom model with phantom stiffness (MEAN/kPa, r=-0.97; AREA/kPa, r=0.98). However, the correlation of RTE and TE was weak in the patient group (MEAN/kPa, r=-0.23; AREA/kPa, r=0.24). A significant difference was observed between the patient and control groups (MEAN, P = 5.32 e-7; AREA, P = 1.62 e-6)., Conclusion: In the phantom model, RTE was correlated with kPa, confirming the presumed comparability of the methods. However, there was no direct correlation between RTE and TE in patients with defined liver diseases under real clinical conditions.

Purpose: To define normal values of liver elasticity measured by real-time tissue elastography (RTE) in healthy infants and children., Methods: RTE was performed on 91 children and adolescents by two experienced observers (female, n = 43; male, n = 48) and in two age groups (0-10 years, n = 45; 11-20 years, n = 46). Hepatopathies were excluded clinically by extensive laboratory testing and by ultrasound. RTE provides a histogram from a region of interest (ROI) in the liver representing the degree of stiffness of the liver. The distribution of the colors in the histogram corresponds to organ elasticity. By calculating the mean of stiffness values, a numerical value is expressed in arbitrary units (a.u.) representing the mean elasticity of the liver (MEAN). Additionally, the percentage values of relatively stiffer areas (color coded in blue) in the ROI can be calculated (%AREA). A Mann-Whitney U test was performed for these two parameters according to gender. The reproducibility of these values was determined with an intraclass correlation coefficient (ICC) test on another group of 18 healthy volunteers., Results: The median elasticity was 106 a.u. Gender did not have an influence on the parameters (MEAN: p = 0.052; %AREA: p = 0.051). Age-specific analyses did not yield any significant difference between the two age groups for either of the two analyzed parameters (MEAN: p = 0.059; %AREA: p = 0.058). The ICC test demonstrated a moderate agreement for MEAN (ICC = 0.582) and %AREA (ICC = 0.659)., Conclusion: Real-time elastography is a new sonography-based method and may be used as a supportive analysis to assess liver parenchyma elasticity in children, especially when fibrosis is suspected. We measured RTE normal values in children as reference data.

Context: There is a need for the discovery of novel natural antioxidants and acetylcholinesterase inhibitors (AChEIs) that are safe and effective at a global level. This is the first study on antioxidant and anti-acethylcholinesterase activity of Scabiosa arenaria Forssk (Dipsacaceae)., Objective: The antioxidant potential and anti-acetylcholinesterase (AChE) activity of S. arenaria were investigated., Material and Methods: The crude, ethyl acetate (EtOAc), butanol (n-BuOH) and water extracts prepared from flowers, fruits and stems and leaves of S. arenaria were tested to determine their total polyphenol content (TPC), total flavonoid content (TFC), total condensed tannin content (CTC) and their antioxidant activity by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), reducing power and β-carotene bleaching inhibition activity. Anti-AChE activity was also determined., Results: EtOAc and n-BuOH fractions of fruits had both the highest (TPC) (269.09 mg gallic acid equivalents/g dry weight). The crude extract of stems and leaves had the highest TFC (10.9 mg quercetin equivalent/g dry weight). The n-BuOH fraction of stems and leaves had the highest CTC (489.75 mg catechin equivalents/g dry weight). The EtOAc fraction of flowers exhibit a higher activity in each antioxidant system with a special attention for DPPH assay (IC50 = 0.017 mg/mL) and reducing power (EC50 = 0.02 mg/mL). The EtOAc and n-BuOH fractions of stems and leaves showed strong inhibition of AChE (IC50 = 0.016 and 0.029 mg/mL, respectively)., Discussion and Conclusions: These results suggest the potential of S. arenaria as a possible source of novel compounds and as an alternative antioxidant and AChEIs.