- Case Report: Treatment of systemic mastocytosis with sunitinib. [Journal Article]
- FF1000Res 2017; 6:2182
- Mast cell activation disease typically presents as chronic multisystem polymorbidity of generally inflammatory ± allergic theme. Presently, treatment of the rare, cytoproliferative variant systemic ...
Mast cell activation disease typically presents as chronic multisystem polymorbidity of generally inflammatory ± allergic theme. Presently, treatment of the rare, cytoproliferative variant systemic mastocytosis employs empirically selected therapies to impede mast cell mediator production and action and, when necessary, inhibition of proliferation. Some tyrosine kinase inhibitors (TKIs) have been used successfully in uncommon cases of systemic mastocytosis not bearing that disease's usual imatinib-resistant KIT D816V mutation. Recently, sunitinib, a multi-targeted TKI, had been successful in a case of systemic mast cell activation syndrome. In addition, most allergy is principally a mast cell activation phenomenon, and sunitinib has been shown helpful in controlling a murine model of oral allergy syndrome. Here, we present the first use of sunitinib in systemic mastocytosis.
- Characterization of phenolic extracts from Brava extra virgin olive oils and their cytotoxic effects on MCF-7 breast cancer cells. [Journal Article]
- FCFood Chem Toxicol 2018 May 15
- The aim of the present work was to evaluate the phenolic profile of the 'Brava' extra virgin olive oil and assess its potential as a "natural adjuvant" in combination with chemotherapy treatment. The...
The aim of the present work was to evaluate the phenolic profile of the 'Brava' extra virgin olive oil and assess its potential as a "natural adjuvant" in combination with chemotherapy treatment. The total phenol content of the phenolic extracts was 764 mg gallic acid equivalents/kg and the total antioxidant capacity was 2309, 1881 and 2088 μM trolox equivalents/kg determined by Diphenyl-1-picrylhydrazyl free radical method, Ferric Reducing Antioxidant Power and Trolox Equivalent Antioxidant Capacity assay, respectively. Secoiridoids comprised 83% of the total phenolic compounds. The main secoiridoid from oleuropein was the main isomer of oleuropein aglycone (74 mg/kg). The main secoiridoid from ligstroside was the main isomer of ligstroside aglycone (214 mg/kg). These phenolic extracts showed a significant decrease in cell viability on MCF-7 breast cancer cells in a dose and time dependent manner. 48 h-treatments with different concentrations of the extracts induced intracellular ROS generation and cell death.
- Preparation of Chitin-PLA laminated composite for implantable application. [Journal Article]
- BMBioact Mater 2017; 2(4):199-207
- The present study explores the possibilities of using locally available inexpensive waste prawn shell derived chitin reinforced and bioabsorbable polylactic acid (PLA) laminated composites to develop...
The present study explores the possibilities of using locally available inexpensive waste prawn shell derived chitin reinforced and bioabsorbable polylactic acid (PLA) laminated composites to develop new materials with excellent mechanical and thermal properties for implantable application such as in bone or dental implant. Chitin at different concentration (1-20% of PLA) reinforced PLA films (CTP) were fabricated by solvent casting process and laminated chitin-PLA composites (LCTP) were prepared by laminating PLA film (obtained by hot press method) with CTP also by hot press method at 160 °C. The effect of variation of chitin concentration on the resulting laminated composite's behavior was investigated. The detailed physico-mechanical, surface morphology and thermal were assessed with different characterization technique such as FT-IR, XRD, SEM and TGA. The FTIR spectra showed the characteristic peaks for chitin and PLA in the composites. SEM images showed an excellent dispersion of chitin in the films and composites. Thermogravimetric analysis (TGA) showed that the complete degradation of chitin, PLA film, 5% chitin reinforced PLA film (CTP2) and LCTP are 98%, 95%, 87% and 98% respectively at temperature of 500 °C. The tensile strength of the LCTP was found 25.09 MPa which is significantly higher than pure PLA film (18.55 MPa) and CTP2 film (8.83 MPa). After lamination of pure PLA and CTP2 film, the composite (LCTP) yielded 0.265-1.061% water absorption from 30 min to 24 h immerse in water that is much lower than PLA and CTP. The increased mechanical properties of the laminated films with the increase of chitin content indicated good dispersion of chitin into PLA and strong interfacial actions between the polymer and chitin. The improvement of mechanical properties and the results of antimicrobial and cytotoxicity of the composites also evaluated and revealed the composite would be a suitable candidate for implant application in biomedical sector.
- Plasma and memory B cell responses targeting O-specific polysaccharide (OSP) are associated with protection against Vibrio cholerae O1 infection among household contacts of cholera patients in Bangladesh. [Journal Article]
- PNPLoS Negl Trop Dis 2018; 12(4):e0006399
- CONCLUSIONS: These results suggest that immune responses that target OSP, both in plasma and memory responses, may be important in mediating protection against infection with V. cholerae O1.
- The inhibitory effect of Manuka honey on human colon cancer HCT-116 and LoVo cell growth. Part 1: the suppression of cell proliferation, promotion of apoptosis and arrest of the cell cycle. [Journal Article]
- FFFood Funct 2018 Apr 25; 9(4):2145-2157
- Numerous investigations have been made on plant phenolic compounds and cancer prevention in recent decades. Manuka honey (MH) represents a good source of phenolic compounds such as luteolin, kaempfer...
Numerous investigations have been made on plant phenolic compounds and cancer prevention in recent decades. Manuka honey (MH) represents a good source of phenolic compounds such as luteolin, kaempferol, quercetin, gallic acid and syringic acid. The aim of this work was to evaluate the chemopreventive effects of MH on human colon cancer HCT-116 and LoVo cells. Both cells were exposed to different concentrations of MH (0-20 mg mL-1 for HCT-116 cells and 0-50 mg mL-1 for LoVo cells) for 48 h to measure apoptosis and cell cycle arrest as well as apoptosis and cell cycle regulatory gene and protein expression. MH exhibited profound inhibitory effects on cellular growth by reducing the proliferation ability, inducing apoptosis and arresting the cell cycle in a dose-dependent manner. Interestingly, MH treatment in non-malignant cells did not exert any significant toxicity at similar concentrations. The apoptosis event was associated with the increasing expression of p53, cleaved-PARP and caspase-3 and with the activation of both intrinsic (caspase-9) and extrinsic (caspase-8) apoptotic pathways. MH induced cell cycle arrest in the S phase in HCT-116 cells, and simultaneously, in LoVo cells, it occurred in the G2/M phase through the modulation of cell cycle regulator genes (cyclin D1, cyclin E, CDK2, CDK4, p21, p27 and Rb). The expression of p-Akt was suppressed while the expression of p-p38MAPK, p-Erk1/2 and endoplasmic stress markers (ATF6 and XBP1) was increased for apoptosis induction. Overall, these findings indicate that MH could be a promising preventive or curative food therapy for colon cancer.
- The inhibitory effect of Manuka honey on human colon cancer HCT-116 and LoVo cell growth. Part 2: Induction of oxidative stress, alteration of mitochondrial respiration and glycolysis, and suppression of metastatic ability. [Journal Article]
- FFFood Funct 2018 Apr 25; 9(4):2158-2170
- Despite its high content of phenolic compounds, the chemopreventive activity of Manuka honey (MH) is still elusive. The aim of the present work was to evaluate the effects of MH on oxidative stress, ...
Despite its high content of phenolic compounds, the chemopreventive activity of Manuka honey (MH) is still elusive. The aim of the present work was to evaluate the effects of MH on oxidative stress, antioxidant enzymes, cellular metabolism and the metastatic ability in HCT-116 and LoVo cells, paying particular attention to the molecular mechanisms involved. We observed a strong induction of oxidative stress after MH treatment since it augmented the accumulation of reactive oxygen species and increased the damage to proteins, lipids and DNA. Furthermore, MH suppressed the Nrf2-dependent antioxidant enzyme expression (superoxide dismutase (SOD), catalase and heme oxygenase-1) and the activity of SOD, catalase, glutathione peroxidase and glutathione reductase. Cell metabolisms were markedly disrupted after MH treatment. It decreased maximal oxygen consumption and spare respiratory capacity, which could reduce the mitochondrial function that is correlated with cell survival potential. Simultaneously, MH decreased the extracellular acidification rate (glycolysis) of HCT-116 and LoVo cells. Furthermore, MH suppressed the p-AMPK/AMPK, PGC1α and SIRT1 activation, involved in the survival of HCT-116 and LoVo cells under metabolic stress conditions. Dose-dependently, MH reduced the migration and invasion (MMP-2 and MMP-9) ability, and concurrently regulated EMT-related markers (E cadherin, N cadherin, and β-catenin) in both cell types. The above findings indicate that MH induces HCT-116 and LoVo cell death partly by enhancing oxidative stress, as well as by regulating the energy metabolism in both aerobic and anaerobic pathways and suppressing the metastatic ability.
- Elucidating the interaction of ticlopidine with serum albumin and its role in bilirubin displacement in vitro. [Journal Article]
- JBJ Biomol Struct Dyn 2018 Mar 15; :1-14
- Ticlopidine is an anti-platelet drug that functions as a P2Y12 receptor antagonist. The present study provides a detailed characterization of interaction of ticlopidine with a model transport protein...
Ticlopidine is an anti-platelet drug that functions as a P2Y12 receptor antagonist. The present study provides a detailed characterization of interaction of ticlopidine with a model transport protein, bovine serum albumin (BSA) as well as an assessment of its bilirubin displacing ability using a multi-spectroscopic approach in combination with isothermal titration calorimetry. The value of binding constant determined using ITC studies was found to be 3.03 × 103 M-1 with a binding stoichiometry of approximately 1:1. Competitive site marker experiments indicate that ticlopidine binds to Sudlow site I, located in subdomain IIA of BSA. In addition, Circular dichroism and 3D fluorescence spectroscopy indicated structural and conformational changes in BSA on interaction with ticlopidine. Thermodynamic parameters suggested that the reaction was spontaneous, exothermic, entropically driven, and involved hydrophobic interactions. These results were well supported by those obtained through molecular docking studies. Additionally, the effect of ticlopidine on bilirubin and albumin interaction was evaluated using the peroxidase method as well as through fluorescence spectroscopy. Ticlopidine was found to displace bilirubin from serum albumin. Moreover, the binding constant of bilirubin-serum albumin interaction also decreased in presence of ticlopidine. The results indicated that ticlopidine is a competitive displacer of bilirubin in vitro and may contribute to the incidences hyperbilirubinemia associated with the usage of this drug.
- Strawberry extracts efficiently counteract inflammatory stress induced by the endotoxin lipopolysaccharide in Human Dermal Fibroblast. [Journal Article]
- FCFood Chem Toxicol 2018; 114:128-140
- A protracted pro-inflammatory state is the common denominator in the development, progression and complication of the common chronic diseases. Dietary antioxidants represent an efficient tool to coun...
A protracted pro-inflammatory state is the common denominator in the development, progression and complication of the common chronic diseases. Dietary antioxidants represent an efficient tool to counteract this inflammatory state. The aim of the present work was to evaluate the effects of strawberry extracts on inflammation evoked by E. Coli lipopolysaccharide in Human Dermal Fibroblast, by measuring reactive oxygen species production, apoptosis rate, antioxidant enzymes activity, mitochondria functionality and also investigating the molecular pathway involved in inflammatory and antioxidant response. The results demonstrated that strawberry pre-treatment reduced intracellular reactive oxygen species levels, apoptotic rate, improved antioxidant defences and mitochondria functionality in lipopolysaccharide -treated cells. Strawberry exerted these protective activities through the inhibition of the NF-kB signalling pathway and the stimulation of the Nrf2 pathway, with a mechanism AMPK-dependent. These results confirm the health benefits of strawberry in the prevention of inflammation and oxidative stress condition in lipopolysaccharide-treated cells.
- Guava (Psidium guajava L. cv. Red Suprema) Crude Extract Protect Human Dermal Fibroblasts against Cytotoxic Damage Mediated by Oxidative Stress. [Journal Article]
- PFPlant Foods Hum Nutr 2018; 73(1):18-24
- We analyzed guava fruits (Psidium guajava L. cv. Red Suprema) from Cuba to determine their chemical composition, total antioxidant capacity, as well as their protective effect against oxidative damag...
We analyzed guava fruits (Psidium guajava L. cv. Red Suprema) from Cuba to determine their chemical composition, total antioxidant capacity, as well as their protective effect against oxidative damage using an in vitro model of human dermal fibroblasts. The guava fruit is a natural source of bioactive compounds, such as polyphenols, vitamin C, folates and beta carotenes with proven health benefits. Human dermal fibroblasts were pre-incubated with different concentrations of guava crude extract and then subjected to oxidative stress using the AAPH stressor. The number of apoptotic and dead cells, as well as the markers of oxidative damage such as lipid and protein oxidation significantly decreased when cells were pre-incubated with guava crude extract and then exposed to the stressor. The activity of antioxidant enzymes also improved when cells were pre-incubated with guava crude extract in comparison to cells subjected to stress without prior pre-incubation with the guava extract. The results obtained in this study highlight the health benefits of guava regarding oxidative stress, proving it to be an important source of bioactive compounds associated with important biological properties.
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- Identification of duck IL-4 and its inhibitory effect on IL-17A expression in R. anatipestifer-stimulated splenic lymphocytes. [Journal Article]
- MIMol Immunol 2018; 95:20-29
- As the dysregulation of IL-17 is implicated in the pathogenesis of various autoimmune and inflammatory diseases, the suppression of IL-17 production by Th2 cytokines could alleviate the development o...
As the dysregulation of IL-17 is implicated in the pathogenesis of various autoimmune and inflammatory diseases, the suppression of IL-17 production by Th2 cytokines could alleviate the development of these diseases. Previously, we confirmed that inflammatory cytokines including IL-17A are strongly associated with R. anatipestifer infection, which is one of the most important bacterial pathogens in the duck industry. Here, we found that IL-4 treatment downregulated the expression of IL-17A and IL-17F transcripts in splenic lymphocytes stimulated with R. anatipestifer. Moreover, duck IL-4 (duIL-4) treatment in R. anatipestifer-stimulated lymphocytes suppressed the expression of IL-23p19 and IL-12p40 transcripts compared to untreated and stimulated lymphocytes. Conversely, duIL-4 increased levels of IFN-γ and IL-10. We identified a full-length duIL-4 cDNA encoding 136 amino acids from ConA-activated splenic lymphocytes that shares 49.3-50% amino acid sequence identity with chicken and quail IL-4 and 21-29.7% with mammalian and piscine homologues. Low or moderate levels of duIL-4 transcript were observed in healthy tissues, including the spleen, bursa, and thymus, whereas duIL-4 expression was higher in the kidney and lung. Levels of duIL-4 were generally upregulated in mitogen-activated splenic lymphocytes but lower in the liver and spleen of R. anatipestifer-infected ducks compared to those of infected chickens. Recombinant duIL-4 promoted nitric oxide synthesis in duck macrophages stimulated by R. anatipestifer compared to untreated and stimulated control macrophages. These results demonstrate that IL-4 is an important Th2 cytokine that inhibits inflammatory responses in splenic lymphocytes stimulated with R. anatipestifer.