CD14 protein as a modulator of the inflammatory response / Bialko CD14 jako modulator odpowiedzi zapalnej.

CD14 is one of the key proteins involved in the activation of the inflammatory response of immune cells. CD14 binds bacterial lipopolysaccharide (LPS) and transfers its molecules to the complex of Toll-like receptor 4 (TLR4) and MD-2 protein, which in turn triggers pro-inflammatory signaling pathways necessary to combat infection. CD14 determines the final shape of the pro-inflammatory reaction of cells to LPS, serving as a transporter of this endotoxin and also as a regulator of TLR4 activity. In addition, CD14 transports other molecules of microbial or endogenous origin to their target receptors/proteins, participating in the activation of pro-inflammatory signaling pathways triggered by the presence of pathogens, as well as tissue damage. Currently, more attention is paid to the role of the CD14 protein in the development of non-infectious diseases such as autoimmune diseases, metabolic diseases and cardiovascular diseases.

Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14.

Lipopolysaccharide (LPS) induces a strong pro-inflammatory reaction of macrophages upon activation of Toll-like receptor 4 (TLR4) with the assistance of CD14 protein. Considering a key role of plasma membrane rafts in CD14 and TLR4 activity and the significant impact exerted on that activity by endocytosis and intracellular trafficking of the both LPS acceptors, it seemed likely that the pro-inflammatory reaction could be modulated by flotillins. Flotillin-1 and -2 are scaffolding proteins associated with the plasma membrane and also with endo-membranes, affecting both the plasma membrane dynamics and intracellular protein trafficking. To verify the above hypothesis, a set of shRNA was used to down-regulate flotillin-2 in Raw264 cells, which were found to also become deficient in flotillin-1. The flotillin deficiency inhibited strongly the TRIF-dependent endosomal signaling of LPS-activated TLR4, and to a lower extent also the MyD88-dependent one, without affecting the cellular level of TLR4. The flotillin depletion also inhibited the pro-inflammatory activity of TLR2/TLR1 and TLR2/TLR6 but not TLR3. In agreement with those effects, the depletion of flotillins down-regulated the CD14 mRNA level and the cellular content of CD14 protein, and also inhibited constitutive CD14 endocytosis thereby facilitating its shedding. Ultimately, the cell-surface level of CD14 was markedly diminished. Concomitantly, CD14 recycling was enhanced via EEA1-positive early endosomes and golgin-97-positive trans-Golgi network, likely to compensate for the depletion of the cell-surface CD14. We propose that the paucity of surface CD14 is the reason for the down-regulated signaling of TLR4 and the other TLRs depending on CD14 for ligand binding.

Analysis of Antioxidant and Antiviral Effects of Olive (Olea europaea L.) Leaf Extracts and Pure Compound Using Cancer Cell Model.

The present study aims to assess the antioxidant and antiviral effectiveness of leaf extracts obtained from Olea europaea L. var. sativa and Olea europaea L. var. sylvestris. The total antioxidant activity was determined via both an ammonium phosphomolybdate assay and a nitric oxide radical inhibition assay. Both extracts showed reducing abilities in an in vitro system and in human HeLa cells. Indeed, after oxidative stress induction, we found that exposition to olive leaf extracts protects human HeLa cells from lipid peroxidation and increases the concentration of enzyme antioxidants such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase. Additionally, OESA treatment affects viral DNA accumulation more than OESY, probably due to the exclusive oleuropein content. In fact, subtoxic concentrations of oleuropein inhibit HSV-1 replication, stimulating the phosphorylation of PKR, c-FOS, and c-JUN proteins. These results provide new knowledge about the potential health benefits and mechanisms of action of oleuropein and oleuropein-rich extracts.

Mechanical Recycling and Its Effects on the Physical and Mechanical Properties of Polyamides.

The aim of this study is to investigate the impact of mechanical recycling on the physical and mechanical properties of recycled polyamide 6 (PA6) and polyamide 66 (PA66) in relation to their microstructures. Both PA6 and PA66 raw materials were reprocessed six times, and the changes in their properties were investigated as a function of recycling number. Until the sixth round of recycling, slight changes in the mechanical properties were detected, except for the percentage of elongation. For the physical properties, the change in both flexural strength and Young's modulus followed a decreasing trend, while the trend in terms of elongation showed an increase. Microscopic analysis was performed on virgin and recycled specimens, showing that imperfections in the crystalline regions of polyamide 6 increased as the number of cycles increased.

Phytochemical composition of Urtica dioica essential oil with antioxidant and anti-inflammatory properties: In vitro and in vivo studies.

Background Urtica dioica (Urticaceae) is distinguished by its therapeutic medicinal and pharmacological properties from all over the world. This investigation was designed toassess the chemical composition, the total polyphenol and flavonoid content, antioxidant, anti-proliferative, and anti-inflammatory effects of Urtica dioica essential oil (UDEO). Methods GC/MS analysis was performed to assess the chemical composition, standard antioxidative test DPPH assay, reducing power assay, as well as the anti-proliferative capacities of UDEO against HeLa cell lines using the MTT test. In addition, the anti-inflammatory activities of UDEO were evaluated using paw thickness measurements in rats with carrageenan-induced paw edema and pathologic evaluation of inflammation in paw sections. Results GC/MS analysis revealed benzene dicarboxylic acid (14.69%), ß-linalool (9.79%), phytol (9.52%), menthol (6.65%), borneol (6.45%), 3-Eicosene (E) (6.10%), 1-8 cineole (5.60%) and camphor (5.36%) as the major components of UDEO. In vitro results showed that UDEO contained 191±2.04 mg GAE/g of polyphenols and 83.59±4.7 mg CE/g of flavonoids. In addition, the UDEO showed radical scavenging activity with IC50 = 0.14±0.003 mg/mL and ferric reducing antioxidant power (FRAP) (optical density=0.556). A side from the UDEO's antioxidant properties, our findings revealed a reduction in ROS generation in the HeLa cell line. Furthermore, the anti-proliferative activity of UDEO is accompanied by acytotoxicity effect (IC50 at 3.20 µg ml-1). Data from inflammation models revealed that UDEO has an anti-inflammatory effect. The pretreatment with UDEO or Indomethacin (Ind) reduced significantly the volume of edema induced by Carr, the level of C-reactive protein (CRP), the reactive thiobarbituric acid (TBARS), the conjugated dienes (CD), the carbonyl proteins (CP) and the advanced protein oxidation products (AOPP). Furthermore, it restored the hematology parameters such as white blood cells (WBC), lymphocytes (LYM), and platelets (PLT). In addition, it increased the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In UDEO-treated rats, the histopathological examinations of the paws revealed little infiltration of inflammatory cells. Conclusion The decrease in paw edema and human cell lines HeLa cytotoxicity showed that UDEO possesses anti-inflammatory and antioxidant properties, which could be attributed to the high amount of phenolic and flavonoid contents.

In Vitro Anti-Epstein Barr Virus Activity of Olea europaea L. Leaf Extracts.

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.

Phytochemical Characterization of Olea europea Leaf Extracts and Assessment of Their Anti-Microbial and Anti-HSV-1 Activity.

Owing to the richness of bioactive compounds, Olea europea leaf extracts exhibit a range of health effects. The present research evaluated the antibacterial and antiviral effect of leaf extracts obtained from Olea europea L. var. sativa (OESA) and Olea europea var. sylvestris (OESY) from Tunisia. LC-DAD-ESI-MS analysis allowed the identification of different compounds that contributed to the observed biological properties. Both OESA and OESY were active against Gram-positive bacteria (MIC values between 7.81 and 15.61 µg/mL and between 15.61 and 31.25 µg/mL against Staphylococcus aureus ATCC 6538 for OESY and OESA, respectively). The antiviral activity against the herpes simplex type 1 (HSV-1) was assessed on Vero cells. The results of cell viability indicated that Olea europea leaf extracts were not toxic to cultured Vero cells. The half maximal cytotoxic concentration (CC50) values for OESA and OESY were 0.2 mg/mL and 0.82 mg/mL, respectively. Furthermore, both a plaque reduction assay and viral entry assay were used to demonstrate the antiviral activity. In conclusion, Olea europea leaf extracts demonstrated a bacteriostatic effect, as well as remarkable antiviral activity, which could provide an alternative treatment against resistant strains.

Antiviral Activity Exerted by Natural Products against Human Viruses.

Viral infections are responsible for several chronic and acute diseases in both humans and animals. Despite the incredible progress in human medicine, several viral diseases, such as acquired immunodeficiency syndrome, respiratory syndromes, and hepatitis, are still associated with high morbidity and mortality rates in humans. Natural products from plants or other organisms are a rich source of structurally novel chemical compounds including antivirals. Indeed, in traditional medicine, many pathological conditions have been treated using plant-derived medicines. Thus, the identification of novel alternative antiviral agents is of critical importance. In this review, we summarize novel phytochemicals with antiviral activity against human viruses and their potential application in treating or preventing viral disease.

In Vitro Anti-HSV-1 Activity of Polyphenol-Rich Extracts and Pure Polyphenol Compounds Derived from Pistachios Kernels (Pistacia vera L.).

Natural compounds are a prominent source of novel antiviral drugs. Several reports have previously shown the antimicrobial activity of pistachio polyphenol extracts. Therefore, the aim of our research was to investigate the activity of polyphenol-rich extracts of natural shelled (NPRE) pistachios kernels (Pistacia vera L.) on herpes simplex virus type 1 (HSV-1) replication. The Vero cell line was used to assess the cytotoxicity and antiviral activity. The cell viability was calculated by detection of cellular ATP after treatment with various concentrations of NPRE. For antiviral studies, five nontoxic-concentrations (0.1, 0.2, 0.4, 0.6, 0.8 mg/mL) were tested. Our study demonstrated that treatment with NPRE (0.4, 0.6, 0.8 mg/mL) reduced the expression of the viral proteins ICP8 (infected cell polypeptide 8), UL42 (unique long UL42 DNA polymerase processivity factor) , and US11 (unique short US11 protein), and resulted in a decrease of viral DNA synthesis. The 50% cytotoxic concentration (CC50), 50% inhibitory concentration (EC50), and the selectivity index (SI) values for NPRE were 1.2 mg/mL, 0.4mg/mL, and 3, respectively. Furthermore, we assessed the anti-herpetic effect of a mix of pure polyphenol compounds (NS MIX) present in NPRE. In conclusion, our findings indicate that natural shelled pistachio kernels have remarkable inhibitory activity against HSV-1.

Lawsonia inermis essential oil: extraction optimization by RSM, antioxidant activity, lipid peroxydation and antiproliferative effects.

BACKGROUND: The present study was focused on the optimization of yield of the essential oil extraction from leaves of Lawsonia inermis, and the determination of chemical composition, antioxidant activities, and lipid peroxydation and antiproliferative effects. METHODS: Henna essential oil (HeEO) were extracted by hydrodistillation; the identification of the chemical composition were done by GC/MS method. HeEO was analyzed for antioxidant power in: (1) chemical system by the DPPH test, the ABTS test and the total antioxidant activity test; and (2) in biological system by lipid peroxydation tests (MDA and DC) in cells culture. The cytotoxicity effects of HeEO were assessed using MTT assay against Raji and HeLa cell lines. RESULTS: The optimal extraction yield was 6.8 g/100 g d.b. HeEO showed a remarkable anti-oxidant activities including DDPH (42%), ABTS (87%) and the power of ammonium phosphomolybdate (2992 ± 230 mg of HeEO by equivalent to 1 mg of vitamin C in terms of total antioxidant power). CONCLUSION: Beyond notable antioxidant activities of the HeEo, our results showed a significant decrease in the production of ERO in the Raji cell line. The anti-tumor power of the Henna essential oil shows an interesting cytotoxicity effect (IC50 at 0.26 µg/mL for Raji and at 1.43 µg/mL for HeLa) with a total mortality percentage reaching 60%, for both.