Purpose: Several studies have suggested that cortisol could be involved in type 2 diabetes (T2D) across different populations. However, this association has not been investigated in the Tunisian population. Our study assessed whether there is a link between T2D and morning blood cortisol levels in diabetic women from Tunisia. Subsequently, a comprehensive meta-analysis was carried out across blood, saliva, and urine samples. Methods: Thirty-three women from southern Tunisia were enrolled in this study. Multivariate logistic regression and receiver operating characteristic (ROC) curve analysis were performed to assess the cortisol-T2D association using R software. In addition, a meta-analysis was conducted using RevMan5.4 software. Besides, a comprehensive search of electronic databases (Google Scholar, PubMed, Scopus, and Circort) was performed. Seventy-three studies reporting baseline cortisol levels in patients diagnosed with T2D and healthy controls were included. The standardized mean difference in cortisol levels was calculated using Random effects model. Results: Morning plasma cortisol levels were significantly higher in T2D cases versus controls (P < 0.001). Multivariate logistic regression, adjusted for age and BMI, confirmed this association (OR 1.021; 95 P<0.00001 ; SMD = 1.4; 95 P<0.0001 ). Notably, T2D patients showed a blunted cortisol awakening response (CAR: SMD = -0.16; 95 P=0.02 ). Conclusion: The logistic regression and the meta-analysis revealed a significant association between high baseline cortisol levels and T2D across blood and saliva. These findings suggest the involvement of elevated baseline cortisol levels in T2D pathogenesis. However, this association needs further investigation.

Pseudomonas aeruginosa elastase LasB accelerates refrigerated food spoilage through proteolytic degradation of muscle and milk proteins. While Marrubium vulgare essential oil terpenes exhibit antimicrobial activity, their weak potency and nonspecificity limit direct food preservation applications. This computational study aimed to rationally redesign terpene scaffolds into predicted selective LasB inhibitors. A virtual library of 635 terpene–peptide–phosphinic acid hybrids (expanded to 3940 conformers) was evaluated using consensus molecular docking (Glide/Flare) against LasB (PDB: 3DBK) and three human off-target proteases. Top candidates underwent duplicate 150 ns molecular dynamics simulations with MM/GBSA binding free-energy calculations. Computational screening identified thymol–Leu–Trp–phosphinic acid as the lead candidate with predicted binding affinity of −12.12 kcal/mol, comparable to reference inhibitor phosphoramidon (−11.87 kcal/mol), and predicted selectivity index of +0.12 kcal/mol representing a 2.3 kcal/mol advantage over human proteases. Molecular dynamics simulations indicated exceptional stability (98.7% stable frames, 0.12 Å inter-replica RMSD) with consistent zinc coordination. Structure–activity analysis revealed phosphinic zinc-binding groups (+1.57 kcal/mol), Leu–Trp linkers (+2.47 kcal/mol), and phenolic scaffolds (+1.35 kcal/mol) as predicted optimal structural features. This in silico study provides a computational framework and prioritized candidate set for developing natural product-derived food preservatives. All findings represent computational predictions requiring experimental validation through enzymatic assays, food model studies, and toxicological evaluation.

Background: Cancer’s multifactorial complexity demands innovative polypharmacological strategies that can simultaneously target multiple oncogenic pathways. Natural products, with their inherent chemical diversity, offer promising multi-target therapeutic potential. This study comprehensively investigates the anticancer mechanisms of Tunisian Myrtus communis essential oils (McEOs) using an integrated computational-experimental framework to elucidate their polypharmacological basis and therapeutic potential. Methods: McEO composition was characterized via GC-MS analysis. Antiproliferative activity was evaluated against HeLa (cervical), MCF-7 (breast), and Raji (lymphoma) cancer cell lines using MTT assays. A multi-scale computational pipeline integrated network pharmacology, molecular docking against eight key oncoproteins, and 100 ns all-atom molecular dynamics simulations to elucidate molecular mechanisms and target interactions. Results: GC-MS revealed a 1,8-cineole-rich chemotype (38.94%) containing significant sesquiterpenes. McEO demonstrated potent differential cytotoxicity: HeLa (IC50 = 8.12 μg/mL) > MCF-7 (IC50 = 19.59 μg/mL) > Raji cells (IC50 = 27.32 μg/mL). Network pharmacology quantitatively explained this differential sensitivity through target overlap analysis, showing higher associations with breast (23%) and cervical (18.3%) versus lymphoma (5.5%) cancer pathways. Molecular docking identified spathulenol as a high-affinity Androgen Receptor (AR) antagonist (XP GScore: −9.650 kcal/mol). Molecular dynamics simulations confirmed exceptional spathulenol-AR complex stability, maintaining critical hydrogen bonding with Asn705 for 96% of simulation time. Conclusions: McEO exerts sophisticated multi-target anticancer effects through synergistic constituent interactions, notably spathulenol’s potent AR antagonism. This integrated computational-experimental approach validates McEO’s polypharmacological basis and supports its therapeutic potential, particularly for hormone-dependent malignancies, while establishing a robust framework for natural product bioactivity deconvolution.

The clinical evidence, complications and the pathogenesis of COVID-19 are not clearly understood. In COVID-19 patients, cellular immune response biomarkers and oxidative stress parameters have been used as gravity markers. Indeed, oxidative stress has been proposed to play an essential role in the genesis of COVID-19. In the present research, we investigated lipid peroxidation, protein oxidation, superoxide dismutase activity and the production of auto-antibodies against superoxide dismutase, in the blood of Tunisian patients with corona virus. To evaluate lipid peroxidation, plasma malondialdehyde and conjugated dienes, have been determined in 69 corona virus patients and 30 controls. To determine protein oxidation the thiol level was measured. Plasma superoxide dismutase activity has been measured in 30 corona virus patients and 30 controls on one hand. Utilizing a standard enzyme-linked immunosorbent assay, the level of immunoglobulin G (IgG), and M (IgM) directed against superoxide dismutase was evaluated. To investigate the implication of auto-antibody production in COVID-19 patients in the generation of oxidative stress, a correlation study between auto-antibodies production and oxidative stress parameters was performed. High levels of both malondialdehyde and conjugated dienes were found in the plasma of patients (p < 0.001, respectively). Protein oxidation was confirmed by the high level of thiol (p < 0.001). Superoxide dismutase activity was not significantly lower in COVID-19 patients (p > 0.05). The level of immunoglobulin G (IgG), and M (IgM) directed against superoxide dismutase is significantly higher in COVID-19 patients than in control group (p < 0.001 respectively). Statistical analyses have demonstrated a positive correlation between superoxide dismutase activity and IgM and IgG isotypes antibodies level against superoxide dismutase (p < 0.001). A strong positive correlation was observed between IgG and malondialdehyde level in all cases (r = 0.368; p ≤ 0.01). In addition, a significant positive correlation was noted between IgM and malondialdehyde (r = 0.290; p = 0.024). Similarly, two significant positive relationship was found between IgG / conjugated dienes (r = 0.356; p = 0.005) and between IgM / conjugated dienes (r = 0.285; p = 0.027).

The widespread use of pesticides, particularly bifenthrin, has raised concerns about their impact on the environment and human health. Bifenthrin has been shown to have adverse effects on male reproductive health, making it a pressing issue to address. In this study, we investigated the potential of Citrus sinensis 'Maltese Half-Blood' essential oil (CsEO) to mitigate bifenthrin-induced testicular toxicity. Our approach combined molecular docking, network pharmacology, histopathology, along with in vitro and in vivo assays. to evaluate the antioxidant properties of CsEO and its ability to counteract bifenthrin's harmful effects. Our results showed that CsEO possesses robust antioxidant attributes, primarily due to its rich phytochemical composition. Limonene, alpha-pinene, and gamma-terpinene were identified as the most contributive compounds. In rat models, CsEO treatment significantly alleviated oxidative stress markers induced by bifenthrin. Network pharmacology analyses revealed the intricate interactions between CsEO's molecular constituents and their biological targets, with compounds like cedrene and geraniol playing key roles. Molecular docking data demonstrated that certain essential oil components have binding affinities to protein targets that rival or even exceed those of bifenthrin. CsEO effectively counteracted bifenthrin-induced testicular oxidative stress, highlighting its therapeutic potential. Our findings provide compelling evidence that CsEO can effectively counteract the harmful effects of bifenthrin on testicular health.

The objectives of this work were to optimize hydro-distillation extraction of Salvia officinalis L. essential oil (SoEO) and to evaluate the in vitro scavenging capacity of the free radicals DPPH · , NO · , ABTS + , and the ability to reduce Fe 3+ . The optimization of SoEO extraction by hydro-distillation was carried out using the response-surface methodology by Box–Behnken. The cytotoxicity and anti-proliferative capacities were evaluated by measuring cell viability and then modeled. Two human tumor cell lines: MCF-7 and HeLa were involved. The obtained optimal extraction yield was Y = 1.85 g/100 g d.b. The main identified fractions were camphene (23.7%), α-thujone (19.62%), 1,8-cineole (10.6%), viridiflorol (5.9%), borneol (5.72%), β-thujone (5.4%) and caryophyllene (3.83%). Also, SoEO was mostly able to scavenge DPPH · free radical, ABTS + radical and hydrogen peroxide in an amount dependent manner (IC 50 = 0.97, 0.279 and 0.05 mg/mL, respectively). All treated cell lines showed a significant reduction in cell viability in response to the increasing of oil concentration. The cytotoxicity activity against both tumor cell lines MCF-7 and HeLa was considerably important with IC 50 = 3.125 and 8.920 μg/mL, respectively. The present work provides a preliminary platform for further investigation of the possible mechanism of S. officinalis essential oils and their individual compounds in cytotoxic and antitumor activities.

Cancer is a significant global health issue with high recurrence rates despite extensive treatments. Hence, the search for new anticancer treatments is of great importance. The purpose of this study was to assess the efficacy of Citrus aurantium peels essential oil (CPEO) as a potential anti-cancer treatment. The Full Factorial Design 23 method was employed to optimize the yield of CPEO extraction and to examine its antioxidant and antiproliferative effects on HeLa and MCF-7 cancer cell lines. GC-MS analysis revealed that limonene is the major constituent of CPEO (68.32%). The optimal extraction yield of 5.47 g/100 g d.b was achieved with a 4-minute microwave pretreatment, 5 washings, and a minimum salt concentration of 175 g/L. The CPEO was endowed with interesting antioxidant activity evaluated by DPPH, H2O2, NO center dot, assays with IC50 of 0.492; 1.120; 1.243 mg/mL respectively. In addition, CPEO exhibited powerful antiproliferative effects evaluated with the MTT assay against HeLa (IC50 of 0.650 mu g/mL) and MCF-7 (IC50 of 1.426 mu g/mL) cell lines. The statistical correlation analyses showed a positive relationship between the IC50 values for MCF-7 and HeLa with the total phenol content (TPC). Based on the molecular docking study, CPEO constituents could dock into the binding pockets of EGFR with energy between -1.695 and -5.052 kcal/mol, As for VEGFR2, energy ranged between -4.175 and -8.096 kcal/mol. Naphthalen-1(2h)-one, limonene, and citral showed an interesting inhibition capacity against EGFR and VEGFR2 by molecular docking study. These findings suggest that CPEO would be a potential natural therapeutic agent for cancer treatment.

BACKGROUND:Citrus fruits have been a valuable economic crop for thousands of years. Furthermore, citrus essential oils are significant in the perfume, food, and beverage sectors, as well as aromatherapy and medical medicines.AIMS:The present study aims to evaluate the phytochemical and pharmacological potentials of the optimized Citrus sinensis 'Maltese half-blood' essential oils peels (CsEO) extraction yields using Response-Surface Methodology (RSM).OBJECTIVE:There have been few investigations on Citrus sinensis 'Maltese half-blood' essential oil.METHODS:Citrus sinensis 'Maltese half-blood' essential oil peels (CsEO) extraction yields were performed by hydro-distillation and optimized by using Response-Surface Methodology (RSM). The oils were analysed by GC-MS. Different chemical tests were used to evaluate antioxidant activities. The healing potential was evaluated using models' wounds on Wistar rats.RESULTS:The RSM optimization demonstrated the highest yield of CsEO of 6.89 g/100 g d.b. All three tested factors significantly influenced the CsEO extraction yield: washing saline solution concentration, washings number, and drying percentage of peels. Significant antioxidant activities were noted in CsEO: the DPPH assay reported an IC50 of 0.225 ± 0.014 mL/mg, the FRAP assay showed an IC50 of 0.235 ± 0.001, and the NO assay was an IC50 in order of 0.259 ± 0.019. CsEO was not genotoxic and considerably decreased the levels of DNA lesions induced by oxidants. Also, applying a cream with CsEO on wounds promotes significantly rapid wound healing.CONCLUSION:CsEO could be considered a rich natural source of antioxidants and bio-compounds to accelerate wound healing. It can be used in pharmaceutical sectors as an alternative to synthetic chemicals.

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 HIF1 & alpha;, 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 HIF1 & alpha; expression, VEGF and HER2 respectively. Nuclear HIF1 & alpha; and VEGF were associated with worst prognosis while cytoplasmic HIF1 & alpha; and HER2 were correlated with favourable prognosis. Multivariate analysis confirms the association between nuclear HIF1 & alpha;, distant metastasis, relapse, FOLFOX response and 5 years overall survival. HIF1 & alpha; positivity and HER2 negativity were significantly associated to short survival. Combined immunoprofiles HIF1 & alpha;+/VEGF+, HIF1 & alpha;+/HER2-, HIF1 & alpha;+/VEGF+/HER2- were associated to distant metastasis, cancer relapse and short survival. Interestingly, our findings confirmed that patients bearing a HIF1 & alpha; positive tumor were significantly more resistant to FOLFOX compared to negative ones (p = 0.002, p & LE; 0.001). Positive expression of HIF1 & alpha; 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 HIF1 & alpha;, alone or combined with VEGF and HER2 serves as a predictive marker of poor prognosis and FOLFOX response in colorectal cancer from south Tunisia.

Background: The contribution of viral infection in tumors pathogenesis has currently attracted attention. EpsteinBarr virus is an infectious agent involved in numerous human malignancies, including breast cancer. Although, their prognostic impact in breast tumor is rarely investigated. Therefore, we sought in our study to evaluate the prevalence of EBV in Tunisian breast carcinoma and to examine their potential association with clinicopathological features and overall survival.Methods: Our retrospective study included 100 formalin fixed paraffin embedded samples from Tunisian breast carcinoma. EBV infection was evaluated by immunohistochemical analysis, using monoclonal antibody against latent membrane protein 1 (LMP-1) and polymerase chain reaction. A subset of PCR positive specimens was subjected to in situ hybridization for the detection of EBER expression. Biomarker's expression was evaluated by immunohistochemistry method. Statistical analysis was also explored. Results: The expression status of ER, PR and HER2 was 81%, 71.4% and 33.7% respectively. The triple negative profile was present in 10.84% of cases. LMP-1 expression was negative in all breast cancer specimens. PCR assay showed that 44% of patients were positive for EBV genome. None of the 15 PCR positive cases showed positive results for EBV by ISH. According to the molecular phenotype, there was a statistically significant difference in EBV DNA prevalence between breast cancer subgroups including TN (67%), Lum B (64%), HER2 + (50%) and Lum A (30%).Bivariate analysis showed that EBV DNA was significantly associated with HER2 + (p = 0.035), tumor size (p = 0.018) and high SBR grade (p = 0.009). Multiple logistic regression analysis confirms the positive correlation of EBV with tumor size (p = 0.048) and SBR grade (p = 0.042). Kaplan-Meier analysis showed that patients with EBV+ had significantly shorter overall survival than those with EBV- (p = 0.032).Conclusions: Our study demonstrated the presence of EBV DNA in Tunisian breast carcinoma. EBV DNA was associated with aggressive features and poor overall survival. Further investigations will be required in large samples size to clarify the potential role of EBV in breast tumor progression.

The current research work attempted to investigate, for the first time, the impact of biochar addition, on anaerobic digestion of olive mill wastewater with different initial chemical oxygen demand loads in batch cultures (10 g/L, 15 g/L, and 20 g/L). Methane yields were compared by applying one-way analysis of variance (ANOVA) followed by post-hoc Tukey’s analysis. The results demonstrated that adding at 5 g/L biochar to olive mill wastewater with an initial chemical oxygen demand load of 20 g/L increased methane yield by 97.8% and mitigated volatile fatty acid accumulation compared to the control batch. According to the results of microbial community succession revealed by the Illumina amplicon sequencing, biochar supplementation significantly increased diversity of the microbial community and improved the abundance of potential genera involved in direct interspecies electron transfer, including Methanothrix and Methanosarcina. Consequently, biochar can be a promising alternative in terms of the recovery of metabolic activity during anaerobic digestion of olive mill wastewater at a large scale.

Punica granatum is a rich source of bioactive compounds which exhibit various biological effects. In this study, pomegranate peel and leaf ethanolic crude extracts (PPE and PLE, respectively) were phytochemically characterized and screened for antioxidant, antimicrobial and antiviral activity. LC-PDA-ESI-MS analysis led to the identification of different compounds, including ellagitannins, flavonoids and phenolic acids. The low IC50 values, obtained by DPPH and FRAP assays, showed a noticeable antioxidant effect of PPE and PLE comparable to the reference standards. Both crude extracts and their main compounds (gallic acid, ellagic acid and punicalagin) were not toxic on Vero cells and exhibited a remarkable inhibitory effect on herpes simplex type 1 (HSV-1) viral plaques formation. Specifically, PPE inhibited HSV-1 adsorption to the cell surface more than PLE. Indeed, the viral DNA accumulation, the transcription of viral genes and the expression of viral proteins were significantly affected by PPE treatment. Amongst the compounds, punicalagin, which is abundant in PPE crude extract, inhibited HSV-1 replication, reducing viral DNA and transcripts accumulation, as well as proteins of all three phases of the viral replication cascade. In contrast, no antibacterial activity was detected. In conclusion, our findings indicate that Punica granatum peel and leaf extracts, especially punicalagin, could be a promising therapeutic candidate against HSV-1.

This paper focuses on the application of the supervised machine learning technique. The main objective is to construct models of objective functions. Sixteen different varieties of benchmark test functions and three well-known engineering design problems are evaluated by machine learning technique. The Artificial Neural Networks (ANNs) technique is used for constructing models. For the sake of accuracy check, three metrics are used; Mean Square Error (MSE), Root Mean Square Error (RMSE) and Maximum Absolute Error (MAE).

Olive pomace is the main by-product generated by the olive oil production process. Although toxic to the environment, olive pomace is an important source of natural antioxidants due to its high content of phenolic compounds. The aim of the current study is to maximize the extraction yields of the main phenolic compounds present in olive pomace using innovative green technologies. For this purpose, the present work is divided into two parts. The first part is based on a solubility study of targeted phenolic compounds in various ethanol/water ratios at two different temperatures (20 °C and 50 °C). A computational prediction using COSMO-RS software was applied for the calculation of eventual solubility, which was subsequently confirmed by practical experiments. The determination of the optimal extraction conditions of solvent ratio (EtOH/H2O) (60:40 v/v) and temperature (50 °C) led to the second part of the work, which concerns the intensification of extraction yields. Furthermore, various green extractions using innovative technologies, including accelerated solvent extraction (ASE), ultrasound with its both system (probe (UAE-P) and bath (UAE-B)), bead milling (BM) and microwave (MAE), were carried out and then compared to conventional maceration (CM). Results showed that ASE was the most effective method for extracting phenolic compounds from dried olive pomace powder (5.3 milligrams of tyrosol equivalent (TE) per gram of dried olive pomace powder (DOP)) compared to CM (3.8 mg TE/g DOP).

Colorectal cancer (CRC) is a commonhealthissue 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 thesemarkers, clinicopathological factors and overall survival of colorectal cancer patients. Marker expression was immunohistochemicallydetermined 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.

Olea europaea L. var. sativa (OESA) preparations are widely used in traditional medicine in the Mediterranean region to prevent and treat different diseases. In this research, olive extracts derived from the leaves of the OESA tree have been screened for antioxidant activity by two methods: the DPPH free radical scavenging assay (DPPH) and the Ferric reducing antioxidant power (FRAP) assay. The DPPH assay showed that OESA possesses a stronger antioxidant activity (84%) at 1 mg/mL while the FRAP method showed a strong metal ion chelating activity (90%) at 1 mg/mL. The low IC50 values, obtained by two different methods, implies that OESA has a noticeable effect on scavenging free radicals comparable to standards. During EBV infection, the free radicals increased triggering lipid oxidation. Therefore, the monitoring of the secondary lipid peroxidation products was done by measuring malonaldehyde (MDA) and conjugated dienes (DC). The simultaneous treatment of Raji cells with OESA and TPA, as an inductorof the lytic cycle, generated a significant decrease in MDA levels and DC (p < 0.05). Besides, Raji cells simultaneously exposed to TPA and OESA exhibited a percentage of EBV-positive fluorescence cells lower than TPA treated cells (**** p < 0.0001). This suggests that OESA treatment has a protective effect against EBV lytic cycle induction.

Cathepsin D (CTSD) is an aspartyl proteinase that plays an important role in protein degradation, antigen processing and apoptosis. It has been associated with several pathologies such as cancer, Alzheimer’s disease and inflammatory disorders. Its function in lung diseases remains, however, controversial. In the current study, we determined CTSD activity in serum of patients with chronic obstructive pulmonary disease (COPD) and evaluated the correlations between this proteinase and inflammatory and oxidative parameters. We also investigated the impact of a CTSD C224T polymorphism on enzyme activity and clinicopathological parameters. Our population included 211 healthy controls and 138 patients with COPD. CTSD activity, MMPs (-1/-7/-12), cytokines (IL-6, TNF-α), malondialdehyde (MDA), nitric oxide and peroxynitrite levels were measured in patients and controls using standard methods. Genotyping of CTSD C224T polymorphism was determined using PCR–RFLP. Our results showed an increased CTSD activity in COPD patients compared to healthy controls (4.87 [3.99–6.07] vs. 3.94 [2.91–5.84], respectively, p < 0.001). COPD smokers presented also a higher CTSD activity when compared to nonsmokers (4.91[3.98–6.18] vs. 4.65[4.16–5.82], respectively, p = 0.01), while no differences were found when subjects were compared according to their GOLD stages. The activity of this proteinase was not dependent on the C224T polymorphism because we did not found any influence of this SNP on proteinase activity among patients and controls. Furthermore, our data provide the first evidence of the interrelationships between CTSD activity and both MMPs and TNF-α levels (MMP-1[r = − 0.4; p = 0.02], MMP-7[r = 0.37; p = 0.04], MMP-12[r = 0.43; p = 0.02], TNF-α [r = 0.89, p = 0.001]) in COPD smokers. There were no correlations, however, between CTSD activity and oxidative stress parameters in controls and patients. Our findings suggest that CTSD could be a relevant marker for COPD disease. Alteration of CTSD activity may be related to increased MMPs and TNF-α levels, particularly in COPD smokers.

Oleaster (Olea europaea var. sylvestris) is a wild olive tree distributed in the Mediterranean area. It is known to possess several biological activities due to their richness in polyphenols. However, enhanced autophagic activity in human cells by using this plant has not been studied before. The objective of the present study was to determine the phytochemical composition of the fruits paste from Tunisian Oleaster, and evaluate its antioxidant activity using the DPPH• and ABTS•+ methods as well as the evaluation of its effect on autophagy activity. The extraction conditions were optimized using response surface methodology (RSM) leading to the best phenolic extract yield. It was noted that ethyl acetate extract presented the highest amount of total phenols and the best solvent for extraction of phenolic compounds. After optimization, the ethyl acetate extract was fractionated into 15 fractions by silica gel column chromatography. The most phenolic components in the fifth and sixth fractions (F5 and F6) were identified using UPLC-ESI(-)-HRMS analysis. Accordingly, F6 was the richer fraction in polyphenols. In vitro antioxidant activity evaluation showed that F6 exhibited a strong ability to scavenge DPPH and ABTS radicals. Furthermore, this fraction was also the most effective to induce autophagic activity in Human foreskin fibroblasts (HFF) cells. These results could be presumably due to the presence of oleuropein aglycon in this fraction which is absent in fraction F5. Oleaster fruits paste would be used as a natural source of bioactive compounds useful in various pharmaceutical drugs.

Background: Olive tree leaves ( Olea europaea ) are widely used in traditional medicine in the Mediterranean Region. Interest in the olive leaf and its chemical constituents has recently been increasing. Its benefits, however, have been known for centuries, and it has been traditionally used to prevent and treat different diseases. The aim of this study was the determination of antimicrobial, antioxidant activities and anti-EBV effects of olive leaves. Methods : The present study was focused on extraction of leaves of olea europea cultivated and wild type from two different geographical tunisian zone: Sfax and El Kef, and the determination of antimicrobial activities against Gram- and Gram+ bacteria and fungi. Olive leaves was analyzed for antioxidant power in chemical system by the DPPH test and the chemiluminescence and in biological system by lipid peroxydation tests (MDA and DC) in Raji cells lines. The antiviral (anti-EBV) effects of olive leaves were assessed using indirect immunofluorescence technique. Results: The antioxidant effect was studied by chemiluminescence where a significant decrease on reactive oxygen species production was observed after leaves olive extract treatment. Antioxidant activities were studied by direct reactive oxyden species assay using chemical systems. The results very interesting for both wild type and cultivated in the two regions since we obtained IC50s of the order of 20.79 μg / ml (cultivated sfax) with DPPH scavening radical. The best result obtained when used olive leaves extract cultivated from Sfax. Our results showed a protection against oxidative stress, highlighted by a significant decrease in MDA and DC levels (p <0.05). Also, a significant antiviral effect of leaves of olive cultivated in Sfax against Epstein-Barr virus (EBV) was determined. Conclusion: The olive leaves extracts analyzed in this work showed a potent antimicrobial activity, an antioxidant activity was expressed by a significant decrease in the production of ERO in the Raji cell line and an anti-EBV effect.

Abstract Background Salvia officinalis L. essential oil (SoEO) was mostly traditionally used to medicate various diseases as cancer. Then, the present work aims were: (1) to model the cytotoxicity effects of Salvia officinalis L. essential oil (SoEO) related to the human cancer cell lines kind (MCF-7 and HeLa) ; (2) to optimize the hydro-distillation extraction conditions of SoEO; and, (3) to determine the in vitro scavenging capacity of the free radicals DPPH•, NO•, ABTS+, and the ability to reduce Fe3+. Methods The cytotoxicity and anti-proliferative abilities were evaluated by measuring cell viability and then modeled. Two human cell lines: MCF-7 and HeLa were used. The optimization of SoEO extraction by hydro-distillation was carried out with Response Surface Methodology (RSM) using the Box–Behnken design Results The cytotoxicity activity against both tumor cell lines MCF-7 and HeLa was considerably important with IC50 = 3.125 and 8.920 µg/mL, respectively. All treated cell lines showed a significant reducing in cell viability in response to the increasing oil concentration. The relative behaviors of both cell lines under SoEO treatment were modeled. The obtained optimal extraction yield was Y = 1.85 g/100 g d.b. The main identified fractions were camphene (23.7%), α-thujone (19.62%), 1,8-cineole (10.6%), viridiflorol (5.9%), borneol (5.72%); β-thujone (5.4%); caryophyllene (3,83%). Also, SoEO was mostly able to scavenge DPPH• free radical, ABTS+ radical and hydrogen peroxide in an amount dependent manner (IC50 = 0.97, 0.279 and 0.05 mg/mL, respectively). Conclusion The present work provides a preliminary platform for further investigation of the possible mechanism of S. officinalis essential oils and their individual compounds in cytotoxic and antitumor activity.