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PurposeTo evaluate the effect of latanoprost 0.005% on the optic nerve head (ONH) and retinal circulation of newly diagnosed and previously untreated primary open-angle glaucoma (POAG) patients.MethodsTwenty-two newly diagnosed and previously untreated POAG patients (mean age±SD: 68.38±11.92 years) were included in this longitudinal open-label study. Patients were treated with latanoprost 0.005% once a day. Intraocular pressure (IOP), systemic blood pressure (BP), mean ocular perfusion pressure (MOPP), and ocular perfusion parameters ‘volume’, ‘velocity’, and ‘flow’ measured at the optic nerve head (ONH) and retina by means of Heidelberg Retina Flowmeter system were evaluated during a 6-month follow-up period.ResultsTreatment with latanoprost 0.005% resulted in a significant decrease in IOP (P<0.0001) and increase in MOPP (P<0.0001). After correcting for changes in MOPP, the blood velocity measured at the ONH level was significantly higher after 6 months of treatment than at baseline (P=0.0310). In addition, blood volume and flow measured at the peripapillary retina level improved after 3 and 6 months of treatment (P=0.0170; P=0.0260, and P=0.0170; P=0.0240 respectively).ConclusionPreviously untreated POAG patients exhibit reduced IOP, increased MOPP and improved ocular perfusion at the ONH and retina levels when treated with Latanoprost 0.005%. These effects could be beneficial for glaucoma patients suffering from ocular vascular dysregulation.Eye (2008) 22, 363–369; doi:10.1038/sj.eye.6702639; published online 17 November 2006 [ABSTRACT FROM AUTHOR]

PURPOSE: To investigate intraocular pressure (IOP) and ocular haemodynamics following small incision cataract surgery. METHODS: Systemic and ocular haemodynamics, and IOP, were measured pre-operatively and 1 month post-operatively, in 25 eyes of 25 patients (mean age 72.6±7.9 years) scheduled for small incision cataract surgery and intraocular lens implantation; these values were compared to an untreated age-matched healthy group (n=25, mean age 72.3±5.0 years). For each eye, the Ocular Blood Flow Analyser (OBFA, Paradigm Inc., UT, USA) was used to obtain measurements of IOP, pulsatile ocular blood flow (POBF), pulse volume (PV), ocular pulse amplitude (PA), and pulse rate (PR). Systemic blood pressure measurements were obtained at each visit. Pre- and post-operative values for the cataract group were compared using repeated measures analysis of variance, and compared to the normal group using analysis of variance. RESULTS: Pre-operatively, IOP was significantly higher in the cataract group compared to the age-matched normal control group (P<0.001). Cataract surgery resulted in a significant 16.7% reduction in IOP (P=0.001). Consequently, the post-operative IOP in the cataract group was similar to that of the normal group (P>0.05). Both pre- and post-operative POBF and PV values for the cataract group were significantly lower than for the normal age-matched group (P<0.0125). Small incision cataract surgery led to an 8.3% post-operative increase in POBF (P=0.0118) and 15.5% increase in PV (P<0.001). No changes in PA or PR were evident. CONCLUSION: These data suggest that cataract patients exhibit higher IOP and reduced ocular perfusion characteristics compared to an age-matched normal healthy group. Following cataract surgery, IOP reduced and ocular pulsatility improved.Eye (2005) 19, 670–675. doi:10.1038/sj.eye.6701620 Published online 3 September 2004 [ABSTRACT FROM AUTHOR]

This study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 µg/mL) and 76.37% (OCNPM-1, 25 µg/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 µg/mL) and 75.15% (OCNPM-3, 25 µg/mL) at the highest dose (25 µg/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 µg/mL) and 58.20% (CLDMM2CP-1 1.25 µg/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy.

Chitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma, and indicates that these molecules can open new perspectives on antiproliferative action and anticancer therapy. This study analyzes how different chitosan conformations, such as α-chitosan (CH) or β-oligochitosan (CO), with various degrees of deacetylation (DDA) and molar mass (MM), both in different concentrations and in CH-CO mixtures, influence the cellular processes of SK-MEL-28 melanocytes, to estimate the reactivity of these cells to the applied treatments. The in vitro evaluation was carried out, aiming at the cellular metabolism (MTT assay), cellular morphology, and chitinase-like glycoprotein YKL-40 expression. The in vitro effect of the CH-CO mixture application on melanocytes is obvious at low concentrations of α-chitosan/β-oligochitosan (1:2 ratio), with the cell's response supporting the hypothesis that β-oligo-chitosan amplifies the effect. This oligochitosan mixture, favored by the β conformation and its small size, penetrates faster into the cells, being more reactive when interacting with some cellular components. Morphological effects expressed by the loss of cell adhesion and the depletion of YKL-40 synthesis are significant responses of melanocytes. β-oligochitosan (1.5 kDa) induces an extension of cytophysiological effects and limits the cell viability compared to α-chitosan (400-900 kDa). Statistical analysis using multivariate techniques showed differences between the CH samples and CH-CO mixtures.

Purpose: This study aims to assess the effect of bariatric surgery on retinal microvascular calibre, peripheral microvascular function, peripheral pressure waveforms, and the general cardiovascular disease (CVD) risk in obese individuals after undergoing Roux-en-Y gastric bypass (RYGB) surgery., Methods: A total of 29 obese participants were included in the study. All of the measurements were conducted at two time points: before and one year following the bariatric surgery procedure. General anthropometric data, as well as blood markers for glucose, cholesterol, and triglycerides were assessed in all individuals. In all participants, the Framingham risk score (FRS), and retinal vessel calibre measurements, using a Zeiss fundus camera and VesselMap software (ImedosSystems, Jena, Germany), were performed. Systemic arterial stiffness was measured by pulse wave analysis (PWA), and peripheral microvascular reactivity by way of digital thermal monitoring (DTM) in all participants., Results: As expected, various general anthropometric parameters, including body mass index (BMI), waist circumference and neck circumference, were significantly decreased post-surgery comparing to baseline in all individuals (all p < 0.001). In addition, their general CVD risk, as measured using FRS, was significantly improved ( p < 0.001). At the retinal vascular level, central retinal artery equivalent (CRAE) as well as, central retinal vein equivalent (CRVE) had increased after surgery comparing to the baseline values ( p = 0.003 and p = 0.007, respectively). In addition, both systemic arterial stiffness and peripheral microvascular reactivity had improved in all participants ( p < 0.001 and p = 0.008 respectively)., Conclusions: Our findings suggest that bariatric surgery has a positive effect on the overall vascular health, as well as on the general CVD risk of the obese patients undergoing this procedure.

In recent years, phytofunctionalized AgNPs have attracted great interest due to their remarkable biological activities. In the present study, AgNPs were synthesized using Abies alba and Pinus sylvestris bark extracts. The chemical profile of these bark extracts was analyzed by LC-HRMS/MS. As a first step, the synthesis parameters (pH, AgNO 3 concentration, ratio of bark extract and AgNO 3 , temperature, and reaction time) were optimized. The synthesized AgNPs were characterized by ATR-FTIR spectroscopy, DLS, SEM, EDX, and TEM. Their antioxidant, cytotoxic, and antibacterial properties were evaluated by the DPPH, ABTS, MTT, and broth microdilution assays, respectively. Abies alba and Pinus sylvestris bark extract-derived AgNPs were well-dispersed, spherical, small (average particle size of 9.92 and 24.49 nm, respectively), stable (zeta potential values of -10.9 and -10.8 mV, respectively), and cytotoxic to A-375 human malignant melanoma cells (IC 50 = 2.40 ± 0.21 and 6.02 ± 0.61 μg/mL, respectively). The phytosynthesized AgNPs also showed antioxidant and antibacterial effects.

The present study aimed to evaluate the morphological, cytogenetic and biochemical changes in wheat seedlings as affected by seed exposure to a proton beam at the Bragg peak. The average energy of the proton beam was of 171 MeV at the entrance into the irradiator room while at the point of sample irradiation the beam energy was of 150 MeV, with the average value of the Linear Energy Transfer of 0.539 keV/μm and the dose rate of 0.55 Gy/min, the radiation doses being of the order of tens of Gy. Cytogenetic investigation has revealed the remarkable diminution of the mitotic index as linear dose-response curve as well as the spectacular linear increase of the aberration index. Analyzing some biometric parameters, it was found that neither dry matter nor water content of wheat seedlings was influenced by proton beam exposure. Studying the biochemical parameters related to the antioxidant defense system, we found that the irradiation caused the slight increasing tendency of peroxidase activity as well as the decreasing trend in the activity of superoxidedismutase in the seedlings grown from the irradiated seeds. The level of malonedialdehyde (MDA) and total polyphenols showed an increasing tendency in all seedling variants corresponding to irradiated seeds, compared to the control. We conclude that the irradiation clearly induced dose-response curves at the level of cytogenetic parameters together with relatively slight variation tendency of some biochemical parameters related to the antioxidant defense system while imperceptible changes could be noticed in the biometric parameters.

Aims: To investigate the microvascular function in apparently healthy individuals showing signs of early macrovascular endothelial dysfunction. Methods: Healthy participants aged between 30−55 years were recruited for the present study. Baseline measurements included body-mass index (BMI), waist-to-hip ratio (WHR), 24-h blood pressure, as well as fasted venous glucose, triglycerides (TG) and cholesterol (HDL, LDL and total). Brachial artery reactivity was measured using the flow-mediated dilation (FMD) technique and retinal vessel reactivity was assessed by using the Dynamic Retinal Vessel Analyser (DVA) in all individuals. The enrolled participants were separated in two groups, based on either a reduced (group 1: <5%—n = 53) or a normal FMD response (group 2: 7−10%—n = 47). Results: Individuals exhibiting reduced FMD responses showed a reduced baseline-corrected microvascular arterial dilation response to flickering light (p = 0.039). In addition, they also exhibited a reduced arteriolar maximum dilation (p = 0.034), as well as a longer dilation reaction time (p = 0.048) and a lower dilation amplitude (p = 0.042) when compared to those with normal FMD values. Conclusion: In otherwise healthy middle-aged individuals, early signs of vascular dysfunction are reflected simultaneously at both macro- and microvascular levels.

Purpose: To assess the similarities and differences in retinal microvascular function between mild Alzheimer’s disease (AD) patients, early-stage primary open angle glaucoma (POAG) patients and healthy controls. Methods: Retinal vessel reactivity to flickering light was assessed in 10 AD, 19 POAG and 20 healthy age matched control patients by means of dynamic retinal vessel analysis (DVA, IMEDOS, GmbH, Jena, Germany) according to an established protocol. All patients additionally underwent BP measurements and blood analysis for glucose and lipid metabolism markers. Results: AD and POAG patients demonstrated comparable alterations in retinal artery reactivity, in the form of an increased arterial reaction time (RT) to flicker light on the final flicker cycle (p = 0.009), which was not replicated by healthy controls (p > 0.05). Furthermore, the sequential changes in RT on progressing from flicker one to flicker three were found to differ between healthy controls and the two disease groups (p = 0.001). Conclusion: AD and POAG patients demonstrate comparable signs of vascular dysfunction in their retinal arteries at the early stages of their disease process. This provides support for the concept of a common underlying vascular aetiology in these two neurodegenerative diseases.

This study aimed to investigate macro- and microvascular function parameters and their relationship with known markers of cardiovascular risk in patients with untreated moderate to severe obstructive sleep apnoea (OSA). Fourteen patients with moderate to severe OSA and fourteen controls were included in the present study. General assessments included BMI, systemic blood pressure (BP) and circulating markers for oxidative stress and endothelial function. Additional assessments included 24 h BP and heart rate monitoring, as well as the assessment of heart rate variability. Macro- and microvascular assessments included augmentation index, carotid intima-media thickness, brachial artery flow-mediated dilation, as well as various retinal microvascular function assessments, using the Dynamic Retinal Vessel Analyzer. All participants completed the Short Form Health Survey, Functional Outcomes of Sleep Questionnaire, and Epworth Sleepiness Scale. The results show that, in comparison to controls, BMI (p = 0.003) and AIx (p = 0.025) were significantly higher in the OSA group. There was, however, no significant difference between groups with regard to other measured systemic general, vascular and circulatory parameters (all p > 0.05). Nevertheless, the retinal microvascular function showed various alterations in the OSA patients, including a delayed reaction time in response to flicker (p = 0.047), as well as a decreased dilation amplitude (p = 0.004), dilation slope (p = 0.004), and post-flicker constriction (p = 0.015). In addition, the observed SlopeAD alterations correlated negatively with BMI values only in the OSA group (r = −0.46, p = 0.045). In conclusion, individuals with untreated moderate to severe OSA but without overt CVD, exhibit signs of increased arterial stiffness and retinal microvascular dysfunction, which can be early indicators for future vascular complications., Competing Interests: The authors declare no conflict of interest.

Ageing represents a major risk factor for many pathologies that limit human lifespan, including cardiovascular diseases. Biological ageing is a good biomarker to assess early individual risk for CVD. However, finding good measurements of biological ageing is an ongoing quest. This study aims to assess the use retinal microvascular function, separate or in combination with telomere length, as a predictor for age and systemic blood pressure in individuals with low cardiovascular risk. In all, 123 healthy participants with low cardiovascular risk were recruited and divided into three groups: group 1 (less than 30 years old), group 2 (31-50 years old) and group 3 (over 50 years old). Relative telomere length (RTL), parameters of retinal microvascular function, CVD circulatory markers and blood pressure (BP) were measured in all individuals. Symbolic regression- analysis was used to infer chronological age and systemic BP measurements using either RTL or a combination of RTL and parameters for retinal microvascular function. RTL decreased significantly with age ( p = 0.010). There were also age-related differences between the study groups in retinal arterial time to maximum dilation ( p = 0.005), maximum constriction ( p = 0.007) and maximum constriction percentage ( p = 0.010). In the youngest participants, the error between predicted versus actual values for the chronological age were smallest in the case of using both retinal vascular functions only ( p = 0.039) or the combination of this parameter with RTL ( p = 0.0045). Systolic BP was better predicted by RTL also only in younger individuals ( p = 0.043). The assessment of retinal arterial vascular function is a better predictor than RTL for non-modifiable variables such as age, and only in younger individuals. In the same age group, RTL is better than microvascular function when inferring modifiable risk factors for CVDs. In older individuals, the accumulation of physiological and structural biological changes makes such predictions unreliable.

The aim of the present research was to assess the effect of bariatric surgery-induced weight loss on the tear film and ocular surface of patients with obesity. A total of 29 participants with obesity (aged 47.2 ± 10.1 years, 8 male) were measured at baseline and followed up one year after Roux-en-Y gastric bypass (RYGB) surgery. General anthropometric data, as well as serum lipid markers of cholesterol, were assessed in all individuals. Bilateral anterior eye measurements of tear meniscus height (TMH), non-invasive tear breakup time, bulbar and limbal redness and infrared meibography were captured using the Keratograph K5M (Oculus) and ocular surface damage was evaluated using fluorescein sodium and lissamine green staining. Bariatric surgery resulted in significant loss of weight (body mass index p < 0.001) and an improvement in the blood lipid profile (p < 0.01) in all participants. However, there were no statistically significant differences between the baseline and one-year follow-up for any of the measured clinical ocular surface and tear film variables (all p > 0.05). Although there were trends for a reduced TMH and a decrease in meibomian gland dropout after bariatric surgery, these differences were also insignificant (p > 0.05). In conclusion, weight reduction through bariatric surgery did not have an effect on the tear film or ocular surface in unselected patients with obesity.

This study aims to complete our research on Usnea barbata (L.) Weber ex F.H. Wigg ( U. barbata ) from the Călimani Mountains, Romania, with an elemental analysis and to explore its antibacterial and antifungal potential. Thus, we analyzed twenty-three metals (Ca, Fe, Mg, Mn, Zn, Al, Ag, Ba, Co, Cr, Cu, Li, Ni, Tl, V, Mo, Pd, Pt, Sb, As, Pb, Cd, and Hg) in dried U. barbata lichen (dUB) by inductively coupled plasma mass spectrometry (ICP-MS). For the second study, we performed dried lichen extraction with five different solvents (ethyl acetate, acetone, ethanol, methanol, and water), obtaining five U. barbata dry extracts (UBDE). Then, using an adapted disc diffusion method (DDM), we examined their antimicrobial activity against seven bacterial species-four Gram-positive ( Staphylococcus aureus , Enterococcus casseliflavus , Streptococcus pyogenes , and Streptococcus pneumoniae ) and three Gram-negative ( Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa )-and two fungi species ( Candida albicans and Candida parapsilosis ). Usnic acid (UA) was used as a positive control. The ICP-MS data showed a considerable Ca content (979.766 µg/g), followed by, in decreasing order, Mg, Mn, Al, Fe, and Zn. Other elements had low levels: Ba, Cu, Pb, and Cr (3.782-1.002 µg/g); insignificant amounts (<1 µg/g) of Hg and V were also found in dUB. The trace elements Ag, As, Cd, Co, Li, Tl, Mo, Pd, Pt, and Sb were below detection limits (<0.1 µg/g). The DDM results-expressed as the size (mm) of the inhibition zone diameter (IZs)-proved that the water extract did not have any inhibitory activity on any pathogens (IZs = 0 mm). Gram-positive bacteria displayed the most significant susceptibility to all other UBDE, with E nterococcus casseliflavus showing the highest level (IZs = 20-22 mm). The most susceptible Gram-negative bacterium was Pseudomonas aeruginosa (IZs = 16-20 mm); the others were insensitive to all U. barbata dry extracts (IZs = 0 mm). The inhibitory activity of UBDE and UA on Candida albicans was slightly higher than on Candida parapsilosis .

The aim of the present paper is to assess the relationship between oxysterol levels and retinal microvascular function in individuals of various age groups, free of clinically evident diseases. Forty-two apparently healthy individuals were included in the present study (group 1: 19-30 years, group 2: 31-50 years, and group 3: 51-70 years). Retinal microvascular function was assessed using the dynamic retinal vessel analyzer (DVA, IMEDOS GmbH, Jena, Germany). Fasting plasma was obtained from all subjects and quantification of monohydroxy and dihydroxy oxysterols assessment was performed using LC-MS/MS following reverse phase chromatography. A Griess assay was used to evaluate the Nitric Oxide (NO) concentration in all individuals. The glutathione redox ratio was also analyzed by means of whole blood glutathione recycling assay. In all participants, the levels of 7-Ketocholesterol, 25-hydroxycholesterol and 7β-hydroxycholesterol correlated significantly and positively with the time to maximum arteriolar dilation. In addition, 25-hydroxycholesterol and 7β-hydroxycholesterol negatively correlated to the percentage of maximum arteriolar dilation. A negative correlation was observed for 27-hydroxycholesterol and 7β-hydroxycholesterol with microvascular arteriolar constriction. These results suggest that, with age, abnormal oxysterol levels correlate with early changes in microvascular bed function. This relationship could signal early risk for cardiovascular diseases (CVDs) in an ageing population.

Purpose: To explore the presence of microvascular endothelial dysfunction as a measure for early cardiovascular disease in individuals diagnosed with dry eye disease (DED) as compared to age-matched normal controls., Methods: Systemic blood pressure, Body Mass Index, intraocular pressure, blood levels of glucose (GLUC), triglycerides, cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] as well as retinal and peripheral microvascular function were assessed in twenty-five 35-50 year olds with diagnosed with DEDa (using the TFOS DEWS II criteria) and 25 age and sex-matched controls., Results: After controlling all the influential covariates, individuals diagnosed with DED exhibited significant lower retinal artery baseline (p = 0.027), artery maximum diameter (p = 0.027), minimum constriction (p = 0.039) and dilation amplitude (p = 0.029) than controls. In addition, the time to reach the vein maximum diameter was significantly longer in the DED patients than in normal controls (p = 0.0052). Only in individuals diagnosed with DED, artery maximum constriction correlated statistically significantly and positively with HDL-C blood levels (p = 0.006). Similarly, artery slope AD correlated positively with T-CHOL and LDL-C (p = 0.006 & 0.011 respectively). Additionally, artery baseline diameter and maximum constriction were significantly and negatively correlated to T-CHOL/HDL-C ratio (p = 0.032 and p = 0.013 respectively) in DED individuals only., Conclusions: Individuals with positive diagnosis of DED exhibit abnormal retinal microvascular function and possible higher risk for CVD., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, Usnea barbata (L) F.H. Wigg ( U. barbata ) and usnic acid (UA) are well-known for their therapeutical properties. One of the most studied properties is their cytotoxicity on various tumor cells. This work aims to evaluate their cytotoxic potential on normal blood cells. Three dry U. barbata extracts in various solvents: ethyl acetate (UBEA), acetone (UBA), and ethanol (UBE) were prepared. From UBEA we isolated usnic acid with high purity by semipreparative chromatography. Then, UA, UBA, and UBE dissolved in 1% dimethyl sulfoxide (DMSO) and diluted in four concentrations were tested for their toxicity on human blood cells. The blood samples were collected from a healthy non-smoker donor; the obtained blood cell cultures were treated with the tested samples. After 24 h, the cytotoxic effect was analyzed through the mechanisms that can cause cell death: early and late apoptosis, caspase 3/7 activity, nuclear apoptosis, autophagy, reactive oxygen species (ROS) level and DNA damage. Generally, the cytotoxic effect was directly proportional to the increase of concentrations, usnic acid inducing the most significant response. At high concentrations, usnic acid and U. barbata extracts induced apoptosis and DNA damage in human blood cells, increasing ROS levels. Our study reveals the importance of prior natural products toxicity evaluation on normal cells to anticipate their limits and benefits as potential anticancer drugs.

Lichens represent an important resource for common traditional medicines due to their numerous metabolites that can exert diverse pharmacological activities including anticancer effects. To find new anticancer compounds with fewer side effects and low tumor resistance, a bioprospective study of Usnea barbata (L.) F.H. Wigg. ( U. barbata ), a lichen from the Călimani Mountains (Suceava county, Romania) was performed. The aim of this research was to investigate the anticancer potential, morphologic changes, wound healing property, clonogenesis, and oxidative stress biomarker status of four extracts of U. barbata in different solvents (methanol, ethanol, acetone, and ethyl acetate), and also of usnic acid (UA) as a positive control on the CAL-27 (ATCC ® CRL-2095™) oral squamous carcinoma (OSCC) cell line and V79 (ATCC ® CCL-93™) lung fibroblasts as normal cells. Using the MTT assay and according to IC 50 values, it was found that the most potent anticancer property was displayed by acetone and ethyl acetate extracts. All U. barbata extracts determined morphological modifications (losing adhesion capacity, membrane shrinkage, formation of abnormal cellular wrinkles, and vacuolization) with higher intensity in tumor cells than in normal ones. The most intense anti-migration effect was established in the acetone extract treatment. The clonogenic assay showed that some U. barbata extracts decreased the ability of cancer cells to form colonies compared to untreated cells, suggesting a potential anti-tumorigenic property of the tested extracts. Therefore, all the U. barbata extracts manifest anticancer activity of different intensity, based, at least partially, on an imbalance in antioxidant defense mechanisms, causing oxidative stress.

Lichens represent a significant source of antioxidants due to numerous metabolites that can reduce free radicals. Usnea barbata (L.) F.H. Wigg. has been recognized and used since ancient times for its therapeutic effects, some of which are based on its antioxidant properties. The present study aims to analyze the phytochemical profile and to evaluate the antioxidant and cytotoxic potential of this lichen species. Five dry extracts of U. barbata (UBDE) in different solvents (acetone, ethyl acetate, ethanol, methanol, water) were prepared by refluxing at Soxhlet to achieve these proposed objectives and to identify which solvent is the most effective for the extraction. The usnic acid content (UAC) was quantified by ultra-high performance liquid chromatography (UHPLC). The total polyphenols content (TPC) and tannins content (TC) were evaluated by spectrophotometry, and the total polysaccharides (PSC) were extracted by a gravimetric method. The 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical method was used to assess the antioxidant activity (AA) and the Brine Shrimp Lethality (BSL) assay was the biotest for cytotoxic activity evaluation. The ethyl acetate extract had the highest usnic acid content, and acetone extract had the highest content of total polyphenols and tannins. The most significant antioxidant effect was reported to methanol extract, and all the extracts proved high cytotoxicity. The water extract has the lowest cytotoxicity because usnic acid is slightly soluble in this solvent, and it was not found at UHPLC analysis. All extracts recorded a moderate correlation between the content of usnic acid, polyphenols, tannins, and AA; furthermore, it has been observed that the cytotoxicity varies inversely with the antioxidant effect.

The present paper examines the effects of salt stress on the growth, pigments, lipid peroxidation and antioxidant ability of barley ( Hordeum vulgare L.) seedlings raised from proton beam irradiated caryopses. In order to assess the effects of radiation on the early stages of plant growth and analyze its possible influence on the alleviation of salinity, 3 and 5 Gy doses were used on dried barley seeds and germination occurred in the presence/absence of NaCl (100 mM and 200 mM). After treatment, photosynthetic pigments increased in the 5 Gy variant, which registered a higher value than the control. Among the antioxidant enzymes studied (SOD, CAT, and POD) only CAT activity increased in proton beam irradiated seeds germinated under salinity conditions, which indicates the activation of antioxidant defense. The malondialdehyde (MDA) content declined with the increase of irradiation doses on seeds germinated at 200 mM NaCl. On the other hand, the concentration of 200 mM NaCl applied alone or combined with radiation revealed an increase in soluble protein content. The growth rate suggests that 3 Gy proton beam irradiation of barley seeds can alleviate the harmful effects of 100 mM NaCl salinity, given that seedlings' growth rate increased by 1.95% compared to the control.

Cancer remains one of the world's most devastating diseases and is responsible for more than 20% of all deaths. It is defined as uncontrolled proliferation of cells and spreads rapidly to healthy tissue. Controlled drug delivery systems offers great opportunities for the development of new non-invasive strategies for the treatment of cancers. The main advantage of these systems is their capacity to accumulate in tumors via enhanced permeability and retention effects. In the present study, an innovative hybrid drug delivery system based on nanocapsules obtained from the interfacial condensation between chitosan and poly(N-vinyl pyrrolidone- alt -itaconic anhydride) and containing both magnetic nanoparticles and an antitumoral drug was developed in order to improve the efficiency of the antitumoral treatment. Using dynamic light scattering, it was observed that the mean diameter of these hybrid nanocapsules was in the range of 43 to 142 nm. SEM confirmed their nanometric size and their well-defined spherical shape. These nanocapsules allowed the encapsulation of an increased amount of 5-fluorouracil and provided controlled drug release. In vitro studies have revealed that these drug-loaded hybrid nanocapsules were able to induce a cytostatic effect on breast carcinoma MCF-7 cell lines (Human Caucasian breast adenocarcinoma - HTB-22) comparable to that of the free drug.

The secondary metabolites of lichens have proven to be promising sources of anticancer drugs; one of the most important of these is usnic acid, which is a phenolic compound with dibenzofuran structure that is responsible for the numerous biological actions of lichens of genus Usnea . As a result, in this study, we related to this phenolic secondary metabolite. The aim of the present study is the evaluation of the cytotoxic activity of Usnea barbata (L.) F. H. Wigg dry acetone extract (UBE). In advance, the usnic acid content was determined in various extracts of Usnea barbata (L.) F. H. Wigg: the liquid extracts were found in water, ethanol, acetone, and the dry acetone extract; the highest usnic acid quantity was found in the dry acetone extract. First, the cytotoxic action of UBE was assessed using Brine Shrimp Lethality (BSL) test; a significant lethal effect was obtained after 24 h of treatment at high used concentrations of UBE, and it was quantified by the high mortality rate of the Artemia salina (L.) larvae. Secondly, in vitro cytotoxicity of UBE was evaluated on human tongue squamous cells carcinoma, using CAL 27 (ATCC ® CRL-2095™) cell line. The most intense cytotoxic effect of UBE on CAL 27 cells was registered after 24 h; this response is directly proportional with the tested UBE concentrations. The obtained results have been reported regarding usnic acid content of UBE, and the data show that CAL 27 cells death was induced by apoptosis and high oxidative stress., Competing Interests: The authors declare no conflict of interest.

The catalytic behavior of iron phthalocyanine (FePc)-sensitized magnetic nanocatalysts was evaluated for their application in the oxidative treatment of Bisphenol A (BPA) under mild environmental conditions. Two types of FePc (Fe(II)Pc and Fe(III)Pc), which are highly photosensitive compounds, were immobilized on the surface of functionalized magnetite. The nanomaterials were characterized by high resolution transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analyses (TGA). The generation of singlet oxygen by nanomaterials was also investigated. In the presence of UVA light exposure (365 nm) and 15 mM H 2 O 2 , the M@Fe(III)Pc photocatalyst gave the best results; for a catalyst concentration of 2.0 g L  - 1 , around 60% BPA was removed after 120 min of reaction. These experimental conditions were further tested under natural solar light exposure, for which also M@Fe(III)Pc exhibited enhanced oxidative catalytic activity, being able to remove 83% of BPA in solution. The water samples were less cytotoxic after treatment, this being confirmed by the MCF-7 cell viability assay.

The current study aims to investigate retinal vascular function and its relationship with systemic anti-oxidative defence capacity in normal individuals versus those with early hypertensive changes according to the current ESC/ESH guidelines. Retinal microvascular function was assessed in 201 participants by means of dynamic retinal vessel analysis. Blood pressure, lipid panel, oxidized (GSH) & reduced glutathione (GSSG) were also evaluated for each participant. Individuals classed as grade 1 hypertension demonstrated higher retinal arterial baseline diameter fluctuation (p = 0.0012), maximum dilation percentage (p = 0.0007), time to maximum constriction (p = 0.0003) and lower arterial constriction slope (p = 0.0131). Individuals classed as high normal and grade 1 hypertension also demonstrated higher time to maximum dilation than individuals classed as optimal or normal. GSH levels correlated negatively with SBP, DBP and MBP values in all participants (p = 0.0010; p = 0.0350 and p = 0.0050) as well as with MBP values in high normal and grade 1 hypertension (p = 0.0290). The levels of GSSG correlated positively with SBP, DBP and MBP values in all participants (p = 0.0410; p = 0.0330 and, p = 0.0220). Our results point to the fact that microvascular alterations can be identifiable at BP values still considered within normal values and go in parallel with the changes observed in the level of oxidative stress.

Objective: To assess retinal and peripheral microvascular function in individuals with low cardiovascular risk., Methods and Results: Retinal microvascular function was assessed using the dynamic vessel analyser (DVA) and peripheral vascular reactivity was measured using the digital thermal monitor (DTM) in 136 healthy participants. In addition, systemic blood pressure (BP) profiles, blood analyses for glucose and lipid metabolism markers (CHOL, HDL-c, LDL-c), as well as the Framingham Risk Score (FRS) were assessed in all participants. Based on peripheral vascular reactivity scores, participants were separated into 3 groups: high, intermediate and low risk. Participants with high risk showed a significant higher retinal arteriolar time to reach maximum dilation (tMD) than those with intermediate and low risk (p < 0.001). In addition, retinal arterial dilation amplitude (DA), and constriction slope (Slope AC ) were higher in subjects with low risk (p = 0.006, p = 0.019). Only in high risk participants, peripheral vascular reactivity parameters correlated with retinal arterial functional parameters DA, (r = 0.3800, p = 0.029) and tMD (r = -0.5904, p < 0.001)., Conclusion: We conclude that signs of abnormal vascular function are similarly present and detectable in various microvascular beds, despite existing differences in their anatomical and physiological properties., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Nanomaterials are being used increasingly in various areas such as electronic devices manufacture, medicine, mechanical devices production, and even food industry. Therefore, the evaluation of their toxicity is mandatory. Graphene oxide (GO) has been shown to have both positive as well as negative impact on different crop plants, depending on species, dose, and duration of exposure. The current study evaluated the impact of GO sheets at different concentrations (500, 1000 and 2000 mg/L) on physiological, biochemical and genetic levels to determine the possible toxic action. Wheat caryopses were treated with GO for 48 h and 7 days. The germination rate and roots elongation decreased in a dose-response manner, except the sample treated with GO at a concentration of 1000 mg/L. Mitotic index has ascendant trend; its increase may be due to the accumulation of prophases GO induced significant accumulation of the cells with aberrations, their presence suggests a clastogenic/aneugenic effect of these carbon nanomaterials. Regarding enzymatic and non-enzymatic antioxidant system defence, the activity varied depending on the dose of GO. Thus, chlorophyll a pigments content decreased significantly at high dose (2000 mg/L), while the carotenoid pigments had lower content at 500 mg/L of GO, and no statistical difference encountered in case of chlorophyll b amount. The antioxidant enzyme activity (CAT, POD, and SOD) was higher at low dose of GO, indicating the presence of oxidative stress generated as a response to the GO treatment. Also, the free radical scavenging activity of the polyphenolic compounds was enhanced upon GO exposure. The GO accumulation has been identified by transmission electron microscopy only at plumules level, near the intercellular space., (Copyright © 2019 Elsevier Inc. All rights reserved.)

New type of nanocapsules based on carboxymethyl chitosan functionalized with AS1411 aptamer and poly(N-vinylpyrrolidone-alt-itaconic anhydride) loaded with 5-Fluorouracil (5-FU) were developed, with the potential to improve the treatment of cancer. Functionalization of nanocapsules with AS1411 aptamer will enhance their recognition by tumor cells, due to the interaction with nucleolin, and subsequent endocytosis. Nanocapsules were prepared by interfacial condensation method in the absence of any toxic crosslinking agents. The condensation reaction took place at the interface between the organic and aqueous phases by opening the anhydride cycles from the copolymer, under the action of the NH 2 groups from mixture of chitosan/aptamer-functionalized carboxymethyl chitosan. The nanocapsules diameter varied between 100 and 267 nm as a function of the molar ratio of the polymers. SEM images have revealed that nanocapsules were spherical and presented relatively low dimensional polydispersity. Nanocapsules swelling degree was found between 1000 and 1680% in PBS solution (pH = 7.4) and they allowed the encapsulation of an important amount of 5-Fluorouracil (5-FU). The release efficiency of 5-FU was studied, the processes being controlled by the drug diffusion through the polymeric membrane, as confirmed by the theoretical analysis of the drug release. The cytotoxicity and haemolysis tests performed on the nanocapsules proved their lack of toxicity and their excellent hemocompatibility. The obtained results were encouraging, showing that these original 5-FU-loaded nanocapsules were able to induce a more pronounced cytotoxic effect on neoplastic MCF-7 cells, the occurrence of dead cells being more rapidly than in the case of free 5-FU., (Copyright © 2019 Elsevier B.V. All rights reserved.)

More than one out of every three new cancers is a skin cancer, and the large majority are basal cell carcinomas (BCC). Targeted therapy targets the cancer's specific genes, proteins, or tissue environment that contributes to cancer growth and survival and blocks the growth as well as the spread of cancer cells while limiting damage to healthy cells. Therefore, in the present study AS1411 aptamer-functionalized liposomes for the treatment of BCC were obtained and characterized. Aptamer conjugation increased liposome size, suggesting that the presence of an additional hydrophilic molecule on the liposomal surface increased the hydrodynamic diameter. As expected, the negatively charged DNA aptamer reduced the surface potential of the liposomes. Vertical Franz diffusion cells with artificial membranes were used to evaluate the in vitro release of 5-fluorouracil (5-FU). The aptamer moieties increase the stability of the liposomes and act as a supplementary steric barrier leading to a lower cumulative amount of the released 5-FU. The in vitro cell viability, targeting capability and apoptotic effects of liposomes on the human dermal fibroblasts and on the basal cell carcinoma TE 354.T cell lines were also evaluated. The results indicate that the functionalized liposomes are more efficient as nanocarriers than the non-functionalized ones.

The aim of this study was to evaluate the performances of Pichia kudriavzevii CR-Y103 yeast strain for the decolorization, biodegradation, and detoxification of cationic dye C.I. Basic Blue 41, a toxic compound to aquatic life with long-lasting effects. Under optimized cultural conditions (10.0-g L -1 glucose, 0.2-g L -1 yeast extract, and 1.0-g L -1 (NH 4 ) 2 SO 4 ), the yeast strain was able to decolorize 97.86% of BB41 (50 mg L -1 ) at pH 6 within 4 h of incubation at 30 °C under shaken conditions (12,238.00-μg h -1 average decolorization rate) and 100% within 12 h. The UV-Vis spectral analysis, high-performance liquid chromatography (HPLC), and Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the complete decolorization and degradation of the BB41 dye by P. kudriavzevii CR-Y103. Also, other seven yeast strains, isolated from soil, as P. kudriavzevii (CR-Y108, CR-Y119, and CR-Y112), Candida tropicalis CR-Y128, Cyberlindnera saturnus CR-Y125, and Candida solani CR-Y124 have shown a promising decolorizing potential of azo-dye BB41 (99.89-76.09% decolorization). Phytotoxicity, cytotoxicity, and genotoxicity assays on Trifolium pratense and Triticum aestivum seedlings confirmed the high toxicity of BB41 dye (500 ppm), with inhibition on germination rate (%), root and shoot elongation, decreasing of mitoxic index value (with 34.03% in T. pratense and 40.25% in T. aestivum), and increasing the frequency of chromosomal aberrations (6.87 times in T. pratense and 6.25 times in T. aestivum), compared to control. The same biomarkers indicated the nontoxic nature of the BB41 degraded metabolite (500 ppm) obtained after P. kudriavzevii CR-Y103 treatment. Moreover, the healthy monkey kidney cells (Vero cells) had a low sensitivity to BB41 biodegraded products (250 μg mL -1 ) (MTT cell viability assay) and revealed minor DNA damage (comet assay) compared to BB41 dye treatment. These findings show that P. kudriavzevii could be used in eco-friendly bioremediation technologies, applicable for reducing the toxicity of basic azo-dyes containing wastewaters.