Multiple sclerosis is a chronic inflammatory neurodegenerative disease of the central nervous system which injures the myelin sheath. Telmisartan and nifedipine are antihypertensive drugs that recently showed neuroprotective properties against neurodegenerative diseases. This study evaluated the neuroprotective effect of telmisartan or nifedipine in cuprizone-induced demyelination in mice by examining the underlying mechanisms. C57BL/6 mice received a diet containing 0.7% (w/w) cuprizone for 7 days followed by 3 weeks on a 0.2% cuprizone diet. Telmisartan (5 mg/kg/day, p.o.) or nifedipine (5 mg/kg/day, p.o.) was administered for 3 weeks starting from the second week. Telmisartan or nifedipine improved locomotor activity and enhanced motor coordination as demonstrated by open field, rotarod, and grip strength tests. Furthermore, telmisartan or nifedipine restored myelin basic protein mRNA and protein expression and increased luxol fast blue-staining intensity. Telmisartan or nifedipine attenuated cuprizone-induced oxidative stress and apoptosis by decreasing brain malondialdehyde and caspase-3 along with restoring reduced glutathione and brain-derived neurotrophic factor levels. Telmisartan or nifedipine exerted an anti-inflammatory effect by reducing the expression of nuclear factor kappa B (NF-κB p65) as well as pro-inflammatory cytokines and elevating the expression of IκB-α. In parallel, telmisartan or nifedipine upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the levels of heme oxygenase-1 and NADPH quinone oxidoreductase 1 enzymes. In conclusion, the current study provides evidence for the protective effect of telmisartan and nifedipine in cuprizone-induced demyelination and behavioral dysfunction in mice possibly by modulating NF-κB and Nrf2 signaling pathways.

Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively). On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%). Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.

A series of quinoline-chalcone hybrids was designed as potential anti-cancer agents, synthesized and evaluated. Different cytotoxic assays revealed that compounds experienced promising activity. Compounds 9i and 9j were the most potent against all the cell lines tested with IC = 1.91-5.29 µM against A549 and K-562 cells. Mechanistically, 9i and 9j induced G/M cell cycle arrest and apoptosis in both A549 and K562 cells. Moreover, all PI3K isoforms were inhibited non selectively with ICs of 52-473 nM when tested against the two mentioned compounds with 9i being most potent against PI3K-γ (IC = 52 nM). Docking of 9i and 9j showed a possible formation of H-bonding with essential valine residues in the active site of PI3K-γ isoform. Meanwhile, Western blotting analysis revealed that 9i and 9j inhibited the phosphorylation of PI3K, Akt, mTOR, as well as GSK-3β in both A549 and K562 cells, suggesting the correlation of blocking PI3K/Akt/mTOR pathway with the above antitumor activities. Together, our findings support the antitumor potential of quinoline-chalcone derivatives for NSCLC and CML by inhibiting the PI3K/Akt/mTOR pathway.

Preparation and evaluation of a non-invasive intranasal luteolin delivery for the management of cognitive dysfunction in Alzheimer's disease (AD) using novel chitosan decorated nanoparticles. Development of luteolin-loaded chitosomes was followed by full in vitro characterization. In vivo efficacy was evaluated using a sporadic Alzheimer's disease (SAD) animal model via intracerebroventricular injection of 3 mg/kg streptozotocin (ICV-STZ). Treatment groups of luteolin suspension and chitosomes (50 mg/kg) were then intranasally administered after 5 h of ICV-STZ followed by everyday administration for 21 consecutive days. Behavioral, histological, immunohistochemical, and biochemical studies were conducted. Chitosomes yielded promising quality attributes in terms of particle size (PS) (412.8 ± 3.28 nm), polydispersity index (PDI) (0.378 ± 0.07), Zeta potential (ZP) (37.4 ± 2.13 mv), and percentage entrapment efficiency (EE%) (86.6 ± 2.05%). Behavioral findings showed obvious improvement in the acquisition of short-term and long-term spatial memory. Furthermore, histological evaluation revealed an increased neuronal survival rate with a reduction in the number of amyloid plaques. Biochemical results showed improved antioxidant effects and reduced pro-inflammatory mediators' levels. In addition, a suppression by half was observed in the levels of both Aβ aggregation and hyperphosphorylated-tau protein in comparison to the model control group which in turn confirmed the capability of luteolin-loaded chitosomes (LUT-CHS) in attenuating the pathological changes of AD. The prepared nanoparticles are considered a promising safe, effective, and non-invasive nanodelivery system that improves cognitive function in SAD albino mice as opposed to luteolin suspension.

Sugar has formed an essential part of human diets for a long time and is an important raw material for the food, beverage and pharmaceutical industries. It is a common name for sucrose and can be extracted from two field crops—sugar beet and sugar cane. Sugar beet (Beta vulgaris ssp. vulgaris) is mainly grown in countries with temperate climates while sugar cane (Saccharum officinarum L.) is cultivated primarily in tropical and subtropical countries. It was demonstrated that sugar beet yield has kept increasing since 1926, but sugar concentration (on fresh weight basis) has not changed much. In the meantime, the improved potential sugar beet yields in the varieties included in the variety trials have been rapidly translated into commercially delivered yields by sugar beet farmers. This can be seen in the increase of farmer-delivered sugar beet yields in parallel with the increase of sugar beet yields in the variety trials. The warming temperature and increasing concentration of CO2 in the atmosphere due to climate change have benefitted the sugar beet crop in recent decades and will probably create opportunities to further boost sugar crop productivity in the future. However, social and environmental demands to adapt sugar beet production to both less input-intensive and less pesticide-dependent cropping systems to mitigate climate change and to maintain biodiversity friendly environments require sugar beet farmers to balance the trade-offs between maximising the sugar yield and increasing the use efficiencies of inputs such as fertilisers, fungicides, pesticides, herbicides and fuels. Sugar beet breeders and other stakeholders need to breed climate-smart cultivars resistant to diseases and find other effective non-chemical solutions to the reduced availability and/or removal of reliable pesticides in the face of more new pathogens emerging under climate change.

Ni–P–TiO2 nanocomposite coatings with various contents of TiO2 nano-particulates were prepared by electroless technique from Ni–P plating bath containing TiO2 powder. X-ray diffractometer (XRD) and energy dispersive X-ray (EDX) technique have been applied in order to investigate the chemical composition and phase structure of the coatings, respectively. The incorporation of TiO2 nano-particulates was found to be improved by the addition of TiO2 powder to the plating bath. However, it has no significant effect on the wt% of P content in the deposit. Scanning electron microscope (SEM) images showed that the morphology of Ni–P–TiO2 nanocomposite coating is finer and smoother than that of Ni–P coating. The catalytic activity of the prepared electrodes toward electro-oxidation of small organic molecules was studied and their stability with time was investigated. The catalytic activity was found to vary with the amount of the TiO2 embedded into the Ni deposit.

The intensive uses of titanium dioxide (TiO2) nanoparticles in sunscreens, toothpaste, sweats, medications, etc. making humans exposed to it daily by not little amounts and also increased its risks including genotoxicity. Thus, the present study was designed as one way to reduce nano-titanium-induced clastogenicity, genotoxicity, and mutagenicity in mice by co-administration of the free radical scavenger chlorophyllin (CHL). In addition, markers of oxidative stress were detected to shed more light on mechanism(s) underlying nano-sized TiO2 genotoxicity. Male mice were exposed to multiple injection into the abdominal cavity for five consecutive days with either CHL (40 mg/kg bw/day), or each of three dose levels of nano-sized TiO2 (500, 1000, or 2000 mg/kg bw/day) alone, or both simultaneously and sacrificed by cervical dislocation 24 h after the last treatment. After CHL co-administration, the observed dose-dependent genotoxicity of TiO2 nanoparticles indicated by the significant elevations in frequencies of both micronuclei and DNA damage induction was significantly decreased and returned to the negative control level. The observed induced mutations in p53 exons 5, 7, & 8 and 5 & 8 in the liver and brain, respectively, were declined in most cases. Moreover, CHL significantly decreased hepatic malondialdehyde level and significantly increased glutathione level and superoxide dismutase, catalase, and glutathione peroxidase activities that were significantly disrupted in animal groups treated with nano-TiO2 alone. In conclusion, the evidenced in vivo genotoxicity of nano-TiO2 in the present study was normalized after CHL co-administration which supports the previously suggested oxidative stress as the possible mechanism for titanium toxicity.

Abstract
BACKGROUND:
Pulsed dye laser has been used successfully in the treatment of nail psoriasis. Intense pulsed light (IPL) has been used in the treatment of plaque psoriasis using a 550-nm filter.
OBJECTIVE:
To study the efficacy of IPL in the treatment of nail psoriasis.
PATIENTS AND METHODS:
Twenty patients with finger and toe nail psoriasis were treated by IPL. Sessions were performed every 2 weeks for a maximum of 6 months. The Nail Psoriasis Severity Index (NAPSI) score was calculated at baseline and 1 month after the last treatment session. Follow-up was performed at 1, 6, and 12 months.
RESULTS:
Patients received a mean of 8.63 ± 3.6 IPL sessions. After treatment, there was significant improvement in the nail bed and matrix (p < .0001), and in the NAPSI (p < .0001). Nail bed showed improvement by 71.2%, whereas the nail matrix improvement was only 32.2%. The total NAPSI was 82.4%. Patient follow-up revealed relapse in 3 patients after 6 months.
CONCLUSION:
Intense pulsed light is a promising effective modality of treatment of nail psoriasis, which is easy to use, safe, and provide a long period of remission. This was confirmed by the elicited clinical improvement, NAPSI, and patient satisfaction.