Green Synthesized Gold and Silver Nanoparticles Increased Oxidative Stress and Induced Cell Death in Colorectal Adenocarcinoma Cells.

The research investigated the effect of gold (Au-CM) and silver nanoparticles (Ag-CM) phytoreduced with Cornus mas fruit extract (CM) on a human colorectal adenocarcinoma (DLD-1) cell line. The impact of nanoparticles on the viability of DLD-1 tumor cells and normal cells was evaluated. Oxidative stress and cell death mechanisms (annexin/propidium iodide analysis, caspase-3 and caspase-8 levels, p53, BCL-2, BAX, NFkB expressions) as well as proliferation markers (Ki-67, PCNA and MAPK) were evaluated in tumor cells. The nanoparticles were characterized using UV-Vis spectroscopy and transmission electron microscopy (TEM) and by measuring zeta potential, hydrodynamic diameter and polydispersity index (PDI). Energy dispersive X-ray (EDX) and X-ray powder diffraction (XRD) analyses were also performed. The nanoparticles induced apoptosis and necrosis of DLD-1 cells and reduced cell proliferation, especially Ag-CM, while on normal cells, both nanoparticles maintained their viability up to 80%. Ag-CM and Au-CM increased the expressions of p53 and NFkB in parallel with the downregulation of BCL-2 protein and induced the activation of caspase-8, suggesting the involvement of apoptosis in cell death. Lipid peroxidation triggered by Ag-CM was correlated with tumor cell necrosis rate. Both nanoparticles obtained with phytocompounds from the CM extract protected normal cells and induced the death of DLD-1 tumor cells, especially by apoptosis.

Neurotoxicity of Bisphenol A and the Impact of Melatonin Administration on Oxidative Stress, ERK/NF-kB Signaling Pathway, and Behavior in Rats.

Bisphenol A (BPA) exposure can be associated with neurodevelopmental disorders due to impairment of cell proliferation and synaptic development. Our study evaluated the effects of melatonin (MEL) on ambulatory activity, lipid peroxidation, cytokines, ERK/NF-kB signaling pathway in the hippocampus and frontal lobe, and histopathological changes in the hippocampus of the BPA-treated rats. The animals were divided into 4 groups: control, BPA, BPA + MEL I, and BPA + MEL II. MEL I (20 mg/kg b.w.) and MEL II (40 mg/kg b.w.) were orally administered for 28 days. On the 29th day, BPA (1 mg/kg b.w.) was intraperitoneally administered, and, after 24 h, an open field test (OFT) and an elevated plus maze (EPM) were conducted. The results showed that the MEL II group made significantly more entries in the open arms of EPM, traveled significantly greater distance, and spent more time in the central part of OFT. Malondialdehyde levels were diminished by MEL II in the hippocampus and by MEL I in the frontal lobe. In the hippocampus, the MAPK level was significantly lowered by both doses of MEL (p < 0.05) while in the frontal lobe, only MEL II reduced the MAPK activation. MEL I and II significantly decreased the γH2AX and upregulated the NFkB and pNFkB expressions in the hippocampus while MEL II downregulated the MCP1 expression. Both doses of MEL attenuated the BPA-evoked histopathological alterations in the hippocampus. These data indicate that MEL can mediate the neuroprotection against BPA-induced neurotoxicity and improves behavioral changes suggesting a real potential as a protective agent in brain toxicity.

Low Doses of Celecoxib Might Promote Phenotype Switching in Cutaneous Melanoma Treated with Dabrafenib-Preliminary Study.

Background: Cutaneous melanoma is a heterogeneous tumor with a rapidly switching molecular and cellular phenotype. The invasive phenotype switching characterized by MITFlow/AXLhigh predicts early resistance to multiple targeted drugs in melanoma. Celecoxib proved to be a valuable adjuvant in cutaneous melanoma in preclinical studies. Our in vitro study evaluated for the first time whether celecoxib could prevent phenotype switching in two human melanoma cell lines treated with dabrafenib. Methods: All in vitro experiments were carried out on BRAF-V600E-positive A375 and SK-MEL-28 human melanoma cell lines, and subjected to a celecoxib and dabrafenib drug combination for 72 h. Melanoma cells were already in the MITFlow/AXLhigh end of the spectrum. Of main interest was the evaluation of the key proteins expressed in phenotype switching (TGF-ß, MITF, AXL, YAP, TAZ), as well as cell death mechanisms correlated with oxidative stress production. Results: Celecoxib significantly enhanced the apoptotic effect of dabrafenib in each melanoma cell line compared to the dabrafenib group (p < 0.0001). Even though celecoxib promoted low MITF expression, this was correlated with high receptor tyrosine kinase AXL levels in A375 and SK-MEL-28 cell lines (p < 0.0001), a positive marker for the phenotype switch to an invasive state. Conclusion: This preliminary study highlighted that celecoxib might promote MITFlow/AXLhigh expression in cutaneous melanoma treated with dabrafenib, facilitating phenotype switching in vitro. Our results need further confirmation, as this finding could represent an important limitation of celecoxib as an antineoplastic drug.

Signet ring cell gastric carcinoma with breast and leptomeningeal metastases: a case report.

Gastric cancer is the 5th most common malignancy worldwide. Signet ring cell histology represents an aggressive subtype of gastric cancer, presenting at a younger age. Both breast and leptomeningeal metastases are rare locations of tumor dissemination, requiring correct and immediate diagnosis and treatment. We present a case of a 45-year old female with signet ring cell gastric carcinoma who developed both left breast and leptomeningeal metastases, requiring multiple chemotherapy lines. As far as we know, this is the first published case in literature following multiple lines of treatment for both breast and leptomeningeal metastases from signet ring cell gastric carcinoma.

Oxidative Stress and DNA Lesion Reduction of a Polyphenolic Enriched Extract of Thymus marschallianus Willd. in Endothelial Vascular Cells Exposed to Hyperglycemia.

The present study aimed to compare two polyphenolic-enriched extracts obtained from the Thymus marschallianus Willd. (Lamiaceae) species, harvested from culture (TMCE in doses of 0.66 µg GAE/mL and 0.066 µg GAE/mL) and from spontaneous flora (TMSE in doses of 0.94 µg GAE/mL and 0.094 µg GAE/mL) by assessing their biological effects on human umbilical vein endothelial cells (HUVECs) exposed to normoglycemic (137 mmol/L glucose) and hyperglycemic conditions (200 mmol/L glucose). Extracts were obtained by solid phase extraction (SPE) and analyzed by chromatographical (HPLC-DAD) and spectrophotometrical methods. Their effects on hyperglycemia were evaluated by the quantification of oxidative stress and NF-ĸB, pNF-ĸB, HIF-1α, and γ-H2AX expressions. The HPLC-DAD analysis highlighted significant amounts of rosmarinic acid (ranging between 0.18 and 1.81 mg/g dry extract), luteolin (ranging between 2.04 and 17.71 mg/g dry extract), kaempferol (ranging between 1.85 and 7.39 mg/g dry extract), and apigenin (ranging between 4.97 and 65.67 mg/g dry extract). Exposure to hyperglycemia induced oxidative stress and the activation of NF-ĸ increased the expression of HIF-1α and produced DNA lesions. The polyphenolic-enriched extracts proved a significant reduction of oxidative stress and γ-H2AX formation and improved the expression of HIF-1α, suggesting their protective role on endothelial cells in hyperglycemia. The tested extracts reduced the total NF-ĸB expression and diminished its activation in hyperglycemic conditions. The obtained results bring evidence for the use of the polyphenolic-enriched extracts of T. marschallianus as adjuvants in hyperglycemia.

Comparative Study of the Pharmacological Properties and Biological Effects of Polygonum aviculare L. herba Extract-Entrapped Liposomes versus Quercetin-Entrapped Liposomes on Doxorubicin-Induced Toxicity on HUVECs.

This study aimed to evaluate the comparative biological effects of Polygonum aviculare L. herba (PAH) extract and quercetin-entrapped liposomes on doxorubicin (Doxo)-induced toxicity in HUVECs. HUVECs were treated with two formulations of liposomes loaded with PAH extract (L5 and L6) and two formulations of liposomes loaded with quercetin (L3 prepared with phosphatidylcholine and L4 prepared with phosphatidylserine). The results obtained with atomic force microscopy, zeta potential and entrapment liposome efficiency confirmed the interactions of the liposomes with PAH or free quercetin and a controlled release of flavonoids entrapped in all the liposomes. Doxo decreased the cell viability and induced oxidative stress, inflammation, DNA lesions and apoptosis in parallel with the activation of Nrf2 and NF-kB. Free quercetin, L3 and L4 inhibited the oxidative stress and inflammation and reduced apoptosis, particularly L3. Additionally, these compounds diminished the Nrf2 and NF-kB expressions and DNA lesions, principally L4. PAH extract, L5 and L6 exerted antioxidant and anti-inflammatory activities, reduced γH2AX formation and inhibited extrinsic apoptosis and transcription factors activation but to a lesser extent. The loading of quercetin in liposomes increased the cell viability and exerted better endothelial protection compared to free quercetin, especially L3. The liposomes with PAH extract had moderate efficiency, mainly due to the antioxidant and anti-inflammatory effects and the inhibition of extrinsic apoptosis.

Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress.

In recent years, escitalopram (ESC) has been suggested to have different mechanisms of action beyond its well known selective serotonin reuptake inhibition. The aim of this study is to investigate the effects of escitalopram on oxidative stress, apoptosis, brain-derived neurotrophic factor (BDNF), Methyl-CpG-binding protein 2 (MeCP2), and oligodendrocytes number in the brain of chronic unpredictable mild stress-induced depressed rats. The animals were randomised in four groups (8 in each group): control, stress, stress + ESC 5 and stress + ESC 5/10. ESC was administered for 42 days in a fixed dose (5 mg/kg b.w.) or in an up-titration regimen (21 days ESC 5 mg/kg b.w. then 21 days ESC 10 mg/kg b.w.). Sucrose preference test (SPT) and elevated plus maze (EPM) were also performed. ESC improved the percentage of sucrose preference, locomotion and anxiety. ESC5/10 reduced the oxidative damage in the hippocampus and improved the antioxidant defence in the hippocampus and frontal lobe. ESC5/10 lowered caspase 3 activity in the hippocampus. Escitalopram had a modulatory effect on BDNF and the number of oligodendrocytes in the hippocampus and frontal lobe and also improved the MeCP2 expressions. The results confirm the multiple pathways implicated in the pathogenesis of depression and suggest that escitalopram exerts an antidepressant effect via different intricate mechanisms.

Ketoconazole-p aminobenzoic cocrystal, an improved antimycotic drug formulation, does not induce skin sensitization on the skin of BALBc mice.

Fungal infections are a growing global health problem. Therefore, our group has synthetized and characterized an improved antimycotic by co-crystallization of ketoconazole and para-amino benzoic acid, named KET-PABA. The aim was to increase bioavailability, biocompatibility, and efficiency of the parent drug-ketoconazole. Based on our previous results showing the cocrystal improved physical properties, such as stability in suspension, solubility, as well as antimycotic efficiency compared to ketoconazole, the current study investigated the local possible side effects induced on the skin of BALBc mice by the application of KET-PABA cocrystal, in view of a further use as a topically applied antimycotic drug. A specific test (mouse ear-swelling test) was used, combined with the histopathological examination and the measurement of pro and anti-inflammatory cytokines and inflammation mediators. KET-PABA application was safe, without signs of skin sensitization shown by the mouse ear sensitization test, or histopathology. KET-PABA strongly inhibited proinflammatory cytokines such as IL1 α, IL1 ß, IL6 and TNF α, and other proinflammatory inducers such as NRF2, compared to vehicle. KET-PABA had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NF-κB pathway. Overall, KET-PABA application induced no sensitization, moreover, it decreased the skin levels of proinflammatory molecules. The lack of skin sensitization effects on BALBc mice skin along with the inhibition of the proinflammatory markers show a good safety profile for topical applications of KET-PABA and show promise for a further clinical use in the treatment of cutaneous mycosis.

Celecoxib as a Valuable Adjuvant in Cutaneous Melanoma Treated with Trametinib.

BACKGROUND: Melanoma patients stop responding to targeted therapies mainly due to mitogen activated protein kinase (MAPK) pathway re-activation, phosphoinositide 3 kinase/the mechanistic target of rapamycin (PI3K/mTOR) pathway activation or stromal cell influence. The future of melanoma treatment lies in combinational approaches. To address this, our in vitro study evaluated if lower concentrations of Celecoxib (IC50 in nM range) could still preserve the chemopreventive effect on melanoma cells treated with trametinib. MATERIALS AND METHODS: All experiments were conducted on SK-MEL-28 human melanoma cells and BJ human fibroblasts, used as co-culture. Co-culture cells were subjected to a celecoxib and trametinib drug combination for 72 h. We focused on the evaluation of cell death mechanisms, melanogenesis, angiogenesis, inflammation and resistance pathways. RESULTS: Low-dose celecoxib significantly enhanced the melanoma response to trametinib. The therapeutic combination reduced nuclear transcription factor (NF)-kB (p < 0.0001) and caspase-8/caspase-3 activation (p < 0.0001), inhibited microphthalmia transcription factor (MITF) and tyrosinase (p < 0.05) expression and strongly down-regulated the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway more significantly than the control or trametinib group (p < 0.0001). CONCLUSION: Low concentrations of celecoxib (IC50 in nM range) sufficed to exert antineoplastic capabilities and enhanced the therapeutic response of metastatic melanoma treated with trametinib.

Biosynthesis of silver nanoparticles using Sambucus nigra L. fruit extract for targeting cell death in oral dysplastic cells.

The study aims to evaluate the impact of silver nanoparticles, phytosynthesized with polyphenols from Sambucus nigra L. (SN) fruit extract (AgSN), on dysplastic oral keratinocytes (DOK) and human gingival fibroblasts (HGF) in terms of cell viability and apoptosis. The morphology and ultrastructure of treated cells as well as the mechanisms involved in cell death induction were investigated in DOK cultures. The structure of AgSN was studied by using the appropriate analysis tools such as UV-Vis, transmission electron microscopy, Raman spectroscopy, dynamic light scattering (DLS) and zeta potential assessment. DOK and HGF were treated either with silver nanoparticles capped with Sambucus nigra L. extract or with SN extract. Untreated cells were used as controls. Viability was determined by MTS assay. Transmission electronic microscopy (TEM) was used to evaluate the intracellular localization of the nanoparticles at 4 and 24 h. Annexin V-FITC/propidium iodide staining and the expressions of p53, BAX, BCL2, NFkB, phosphorylated NFkB (pNFkB), pan AKT, pan phosphoAKT, LC3B and É£H2AX were evaluated to quantify the cell death. ELISA measurements of TNF-α and TRAIL was used for the study of the inflammatory response. Oxidative stress damage induced by nanoparticles was assessed by the malondialdehyde (MDA) level. Silver nanoparticles stimulated HGF proliferation and significantly diminished DOK viability at doses higher than 20 µg/ml. TEM analysis demonstrated the internalization of silver nanoparticles and showed ultrastructural changes of cells such as the appearance of vacuoles, autophagosomes, endosomes. AgSN inhibited the pro-survival molecules and regulators of apoptosis, diminished oxidative stress and inflammation and induced cell death through various mechanisms: necrosis, autophagy and DNA lesions. SN extract had antioxidant and anti-inflammatory effect and increased the DNA lesions and autophagy in DOK cells. Silver nanoparticles protected the normal cells and induced cell death in dysplastic cells by different mechanisms thus offering beneficial effects in the treatment of oral dysplasia.

The impact of silver nanoparticles phytosynthesized with Viburnum opulus L. extract on the ultrastrastructure and cell death in the testis of offspring rats.

AIM: To investigate the effects of prenatal exposure to AgNPs obtained by green synthesis with Viburnum opulus L. extract on the testis in male offspring rats. MATERIAL AND METHODS: Two different doses of AgNPs (0.8 and 1.5 mg/kg b.w.) and vehicle (PBS) were administered to Wistar female rats on days 3-14 of gestation. At 6 weeks after birth, the ultrastructural changes in correlation with the amount of silver as well as the parameters of oxidative stress, inflammation and cell death mechanisms in the testis of male offspring were evaluated. RESULTS: AgNPs administered during pregnancy crossed the placental and testicular barriers and induced oxidative stress, DNA damage and autophagy as mechanism of cell toxicity. The markers of inflammation and apoptosis decreased after AgNPs exposure while the NFkB activation increased. TEM examination revealed important ultrastructural changes of Sertoli cells, numerous vacuoles and cytoplasmic changes suggestive of the cell's evolution towards necrosis. CONCLUSION: Phytoreduced silver nanoparticles with polyphenols from Viburnum opulus L. fruit extract, administered during the embryological development of the male gonad, have testicular toxic effects in offspring even at 6 weeks after birth.

Genetic predisposition in pediatric oncology.

Identifying patients with a genetic predisposition for developing malignant tumors has a significant impact on both the patient and family. Recognition of genetic predisposition, before diagnosing a malignant pathology, may lead to early diagnosis of a neoplasia. Recognition of a genetic predisposition syndrome after the diagnosis of neoplasia can result in a change of treatment plan, a specific follow-up of adverse treatment effects and, of course, a long-term follow-up focusing on the early detection of a second neoplasia. Responsible for genetic syndromes that predispose individuals to malignant pathology are germline mutations. These mutations are present in all cells of conception, they can be inherited or can occur de novo. Several mechanisms of inheritance are described: Mendelian autosomal dominant, Mendelian autosomal recessive, X-linked patterns, constitutional chromosomal abnormality and non-Mendelian inheritance. In the following review we will present the most important genetic syndromes in pediatric oncology.

Targeting Oxidative Stress Reduction and Inhibition of HDAC1, MECP2, and NF-kB Pathways in Rats With Experimentally Induced Hyperglycemia by Administration of Thymus marshallianus Willd. Extracts.

The effects of two lyophilized extracts obtained from the aerial parts of Thymus marschallianus Willd. and harvested from wild flora (TMW) and obtained from culture (TMC) were evaluated in Wistar rats with experimentally induced hyperglycemia. The hyperglycemia was induced by streptozotocin (STZ) administration and the obtained results were evaluated in comparison for TMW and TMC. The polyphenolic composition of extracts was evaluated by spectrophotometrical and LC-MS methods. In vitro antioxidant capacity assays (DPPH, FRAP, EPR) were performed in order to preliminary establish the ability of tested samples to protect against free radical induced damage. Afterwards, the effects of these extracts were assessed in vivo on rats with experimental-induced hyperglycemia. Oxidative stress biomarkers (e.g. malondialdehyde-MDA), phosphorylated transcription factor subunit of nuclear kappaB (NF-kB) p65, methyl CpG binding protein (MECP) 2 and histone deacetylase 1 (HDAC1) expressions in hippocampus and frontal lobe were assessed. Open Field Test (OFT) and Elevated Plus Maze (EPM) were conducted on tested animals. Malondialdehyde (MDA) levels and HDAC1and MeCP2 expressions increased significantly in hippocampus (p<0.05) and frontal lobe (p<0.001) of diabetes group compared to the control group in parallel with decreasing of GSH/GSSG ratio. TMW and TMC administration reduced blood glucose levels and diminished lipid peroxidation, HDAC1 expression and enhanced antioxidant capacity in frontal lobe. TMW improved central locomotion of rats, increased phospho-NFkB p65 and diminished MECP2 expressions in hippocampus. Both tested samples exerted a beneficial effect by increasing the antioxidant defense. Our findings indicate that the administration of these extracts might represent a good option in the treatment of diabetes and its complications.

Physalis alkekengi L. Extract Reduces the Oxidative Stress, Inflammation and Apoptosis in Endothelial Vascular Cells Exposed to Hyperglycemia.

To find new natural remedies in diabetes, this study investigated the biological activity of two extracts obtained from the fruits (PhyF) and herba (PhyH) of Physalis alkekengi var. franchetii L. on human umbilical vein endothelial cells (HUVECs) exposed to normo- and hyperglycemic conditions. The biological effect was quantified by malondialdehyde, IL-31 and IL-33 levels in correlation with physico-chemical characterization and antioxidant activity. Additionally, from PhyP extract, the caspase-3, IL-6, IL-10, tumor necrosis factor (TNF)-α and nuclear transcription factor NFkB expressions were evaluated. HPLC analysis revealed a significant number of phenolic compounds, especially in PhyF extract, with a good antioxidant activity as highlighted by TEAC, CUPRAC or DPPH methods. On HUVECS cells, the extracts were not toxic even at high concentrations. Particularly PhyF extract, diminished lipid peroxidation and inhibited the IL-31 and IL-33 secretions induced by hyperglycemia. The inhibitory effect on proinflammatory cytokines was noticed after both doses of PhyF extract in parallel with the upregulation of anti-inflammatory cytokine IL-10. Moreover, PhyF, especially in a low dose, reduced caspase-3 active form. These experimental findings suggest that Physalis fruits extract exerted beneficial effects in hyperglycemia by inhibition of oxidative stress, inflammation and apoptosis being a good adjuvant option in diabetes.

Hepatoprotective effects of silymarin coated gold nanoparticles in experimental cholestasis.

The present study reports the green synthesis of hybrid organic-inorganic gold nanocomposites using silymarin as reducing and capping agent. The structure of the silymarin loaded gold nanoparticles was investigated by using the appropriate analysis tools such as UV-Vis and Fourier-transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM) techniques. TEM micrographs demonstrated that the gold nanoparticles were spherical in shape, well distributed and their mean size was about 10 nm. The in vivo hepatoprotective and antifibrogenic properties after bile duct ligation in rats of the silymarin coated gold nanoparticles were assessed. The changes regarding the blood tests and the liver histopathology were compared to the standard administration of silymarin. Silymarin loaded gold nanoparticles improved liver function, reduced cholestasis and oxidative stress parameters, with the increase of antioxidant support, and reduced inflammation and fibrosis in the liver of rats with extrahepatic cholestasis.

The Modulatory Effect of Metformin on Ethanol-Induced Anxiety, Redox Imbalance, and Extracellular Matrix Levels in the Brains of Wistar Rats.

The study investigated the potential neuroprotective effects of metformin (MET) on alcohol-induced neurotoxicity in adult Wistar rats. The animals were randomized in four groups (n = 10): control, alcohol (ALC), ALC + MET, and MET. ALC (2 g/kg b.w.) and MET (200 mg/kg b.w.) were orally administered for 21 days, once daily. For the ALC + MET group, MET was administered 2 h after ALC treatment. On day 22, the open field test (OFT) and elevated plus maze (EPM) were performed. MET improved global activity and increased the time spent in unprotected open arms, decreased oxidative stress, both in the frontal lobe and in the hippocampus, and increased neuroglobin expression in the frontal cortex. Histopathologically, an increased neurosecretory activity in the frontal cortex in the ALC + MET group was noticed. Thus, our findings suggest that metformin has antioxidant and anxiolytic effects and may partially reverse the neurotoxic effects induced by ethanol.

A Phytocomplex Consisting of Tropaeolum majus L. and Salvia officinalis L. Extracts Alleviates the Inflammatory Response of Dermal Fibroblasts to Bacterial Lipopolysaccharides.

BACKGROUND: The antimicrobial activity and effects of a phytocomplex consisting of Tropaeolum flos (T) and Salviae folium (S) extracts on the cytokine levels and transcription factors on dermal fibroblast BJ exposed to bacterial lipopolysaccharides were examined. METHODS: In order to select the most optimal combination ratio of the two extracts for using in vitro, the physicochemical characterization of vegetal extract mixtures was performed and the antioxidant and antibacterial activities were evaluated on five different formulations of T : S, namely, 1 : 1, 1 : 2, 2 : 1, 3 : 1, and 1 : 3. The best combination of bioactive compounds with regard to antioxidant and antibacterial activities (T : S 1 : 2) was selected for in vitro evaluation of the anti-inflammatory effect. Human dermal fibroblast BJ cells were treated with two doses of the extract mixture and then exposed to bacterial lipopolysaccharides (LPS). The levels of the cytokines involved in inflammatory response, namely, interleukin- (IL-) 6, tumor necrosis factor- (TNF-) α, IL-31, and IL-33, were quantified by ELISA, and the expression of transcription factors, namely, signal transducer and activator of transcription (STAT) 3, nuclear factor kappa B (NFκB), and phosphorylated NFκB (pNFκB), were evaluated by western blot analysis. RESULTS: The results have shown that the mixture of T : S 1 : 2 exhibited significant antibacterial effects on Staphylococcus aureus ATCC 25923. LPS exposure increased the cytokine levels in BJ cells and enhanced the NFκB expression. The pretreatment of BF cells exposed to LPS with the two doses of the extract mixture markedly inhibited the increase of IL-33 and TNF-α levels and amplified the NFκB expression and its activation, especially with the high dose. The low doses of the extract reduced NFκB expression but increased its activation. CONCLUSIONS: These experimental findings suggest that the mixture of T : S 1 : 2 can exert some protection against bacterial infections and inflammation induced by LPS in BJ cells being a good therapeutic option in related conditions associated with inflammation.

Modulatory effects of Cornus sanguinea L. mediated green synthesized silver nanoparticles on oxidative stress, COX-2/NOS2 and NFkB/pNFkB expressions in experimental inflammation in Wistar rats.

The present study presents a green, cost efficient and easy synthesis method of silver nanoparticles (AgNPs) using an aqueous extract of Cornus sanguinea L. fruits (CS). The phytosynthesized silver nanoparticles were characterized using various analytical techniques such as UV-Vis absorption spectroscopy, which confirmed the formation of AgNPs and FTIR spectroscopy, in order to certify the role of the biomolecules present in the fruit extract as reducing and capping agents of the AgNPs. The UV-Vis absorption spectrum showed a broad band at 407 nm characteristic for colloidal silver. Transmission electron microscopy was conducted to investigate the shape and size of the silver nanoparticles, revealing a spherical shape with an average particle size of 18 nm. The antioxidant and anti-inflammatory activities of the fruit extract and green synthesized silver nanoparticles were assessed in vivo on experimental inflammation. The obtained results showed that CS and AgNPs reduced oxidative stress in parallel with increasing of antioxidant defense and diminished the COX-2 expressions. CS extract had a dual effect on NFkB activation depending on the time of testing while AgNPs increased NFkB phosphorylation at 48 h. These results suggested that both AgNPs and CS extract exhibited antioxidant and anti-inflammatory activities but with a different dynamics of action.

The in vivo modulatory effects of Cornus mas extract on photodynamic therapy in experimental tumors.

BACKGROUND: Photodynamic therapy (PDT) is a treatment of cancer due to its ability to induce cell death, oxidative stress and acute inflammatory reaction in targeted sites. To optimize the effect of PDT the addition of some compounds with supplementary cytotoxic effect on tumor cells was tried. METHODS: The study was performed on 35 Wistar male albino rats with Walker 256 carcinosarcoma. The animals were randomly assigned in seven groups (n = 5) and treated as follows: group 1 - control; group 2 - Cornus mas (CM) extract 15 mg/kg b.w., administered for 7 days; group 3 - CM extract administered for 7 days followed by irradiation (CM + IR); group 4 - one dose of tetra-p-sulfonato-phenyl-porphyrin (TSPP) 10 mg/kg b.w.; group 5 - TSPP + IR; group 6 - CM extract administered daily for 7 days before TSPP and IR (CM + TSPP + IR); group 7 - TSPP + IR followed by CM administered for 7 days (TSPP + IR + CM). RESULTS: The results showed that MDA and GSSG levels increased after PDT in parallel with the increasing of COX-2 expression and DNA damage. Apoptotic and necrotic index enhanced in TSPP + IR, effect improved by CM association before PDT. CM + TSPP + IR regimen also induced more intense inflammatory reactions, increased COX-2 expression, determined DNA damage, apoptosis and necrosis, compared to the TSPP + IR + CM group. Both combined therapeutic regimens reduced MDA levels in tumor tissue, especially CM + TSPP + IR and increased the antioxidant defense and iNOS expression. CONCLUSIONS: Our results demonstrated that CM associated before PDT had beneficial effects in PDT and may represent a promising option in PDT strategies.

Flexural strength, biocompatibility, and antimicrobial activity of a polymethyl methacrylate denture resin enhanced with graphene and silver nanoparticles.

OBJECTIVE: The study evaluates the effect of adding graphene-Ag nanoparticles (G-AgNp) to a PMMA auto-polymerizing resin, with focus on antibacterial activity, cytotoxicity, monomer release, and mechanical properties. MATERIALS AND METHODS: Auto-polymerizing acrylic resin (M) was loaded with 1 wt% G-AgNp (P1) and 2 wt% G-AgNp (P2). Methyl methacrylate monomer release (MMA) was measured after immersion of the samples in chloroform and cell medium respectively. Cell viability was assessed on dysplastic oral keratinocytes (DOK) and dental pulp stem cells. Oxidative stress and inflammatory response following exposure of dysplastic oral keratinocytes to the experimental resins was evaluated. Antibacterial activity against Staphylococcus aureus, Streptococcus mutans and Escherichia coli and also flexural strength of the resins were assessed. RESULTS: Residual monomer: For samples immersed in chloroform, MMA concentration reached high levels, 10.27 µg/g for sample P1; MMA increased at higher G-AgNp loading; 0.63 µg/g MMA was found in medium for P1, and less for sample P2. Cell viability: Both cell lines displayed a viability decrease, but remained above 75%, compared to controls, when exposed to undiluted samples. Inflammation: proinflammatory molecule TNF-α decreased when DOK cultures were exposed to G-AgNp samples. MDA levels indicated increased oxidative stress damage in cells treated with PMMA, confirmed by the antioxidant mechanism activation, while samples containing G-AgNp induced an antioxidant effect. All tested samples showed antibacterial properties against Gram-positive bacteria. Samples containing G-AgNp also exhibited bactericide action on E. coli. Mechanical properties: both samples containing G-AgNp improved flexural strength compared to the sample resin, measured through elastic strength parameters. CONCLUSIONS: PMMA resin loaded with G-AgNp presents promising antibacterial activity associated with minimal toxicity to human cells, in vitro, as well as improved flexural properties. CLINICAL RELEVANCE: These encouraging results obtained in vitro support further in vivo investigation, to thoroughly check whether the PMMA loaded with graphene-silver nanoparticles constitute an improvement over current denture materials.