Chondroitin/Lactoferrin-dual functionalized pterostilbene-solid lipid nanoparticles as targeted breast cancer therapy.

Breast cancer remains the leading cause of cancer-associated mortality in women. Research investigating novel therapeutic approaches is thus crucial, including phytotherapeutics. Pterostilbene (PTS) is a phytochemical agent with promising efficacy against breast cancer. Poor solubility, low bioavailability and chemical instability are major drawbacks compromising PTS functionality. Herein, novel PTS-loaded solid lipid nanoparticles (PTS-SLNs) were fabricated using the ultrasonication technique. Dual-functionalization with lactoferrin (Lf) and chondroitin-sulfate (CS; CS/Lf/PTS-SLNs) was adopted as active-targeting approach. CS/Lf/PTS-SLNs demonstrated nanoparticle-size (223.42 ± 18.71 nm), low PDI (0.33 ± 0.017), acceptable zeta potential (-11.85 ± 0.07 mV) and controlled release (72.93 ± 2.93% after 24 h). In vitro studies on triple-negative MDA-MB-231 revealed prominent cytotoxicity of CS/Lf/PTS-SLNs (2.63-fold IC50 reduction), higher anti-migratory effect and cellular uptake relative to PTS-solution. The in vivo anti-tumor efficacy in an orthotopic cancer model verified the superiority of CS/Lf/PTS-SLNs; achieving 2.4-fold decrease in tumor growth compared to PTS-solution. On the molecular level, CS/Lf/PTS-SLNs enhanced suppression of VEGF, down-regulated cyclin D1 and upregulated caspase-3 and BAX, compared to PTS-solution. Also, immunohistochemical assay confirmed the higher anti-tumorigenic effect of CS/Lf/PTS-SLNs (5.87-fold decrease in Bcl-2 expression) compared to PTS-solution. Our findings highlight CS/Lf/PTS-SLNs as a promising nanoplatform for phytotherapeutic targeted-breast cancer therapy.

Protective effect of sitagliptin and whole-body γ-irradiation in diabetes-induced cardiac injury.

Diabetes mellitus is associated with an increased risk of cardiac complications; this study aimed to investigate effect of sitagliptin (SITA) alone or combined with γ-irradiation on diabetes-associated cardiac injury. Rats were treated with SITA (100 mg/kg per day; p.o.) for 2 weeks followed by a single dose of whole-body γ-irradiation (3 Gy). Solitary administration of SITA or combined treatment with γ-irradiation succeeded to ameliorate the increase in serum levels of glucose, total cholesterol, triglycerides, creatine kinase-MB, and malondialdehyde, coupled by increased insulin and reduced glutathione levels. Their cardioprotective potential was confirmed through attenuating the apoptotic signaling by mitigating Bcl-2-associated X protein, caspase-3, and apoptosis-inducing factor expression, while augmenting the anti-apoptotic factors, B cell lymphoma-2 (Bcl-2), and heat shock protein 70 (HSP-70) in left ventricular tissue homogenates. These findings were supported histopathologically. In conclusion, treatment with SITA alone or combined with γ-irradiation may prove beneficial in diabetes-accompanied cardiac insult. This could be due to the crosstalk between the antioxidant, anti-apoptotic, and restoration of body's defense capacities.

Genetic Diversity among Selected Medicago sativa Cultivars Using Inter-Retrotransposon-Amplified Polymorphism, Chloroplast DNA Barcodes and Morpho-Agronomic Trait Analyses.

Alfalfa (Medicago sativa L.) is a major forage crop of family Fabaceae and is frequently cultivated in Egypt. The present study is concerned with the genetic discrimination of fifteen alfalfa cultivars from three different countries (Egypt, Australia, and USA) using two molecular approaches: inter-retrotransposon-amplified polymorphism (IRAP) markers and two chloroplast DNA barcodes matK and the trnH in addition to the analysis of fifteen morpho-agronomic traits. The genetic relatedness, based on analysis of IRAP marker polymorphism and produced using eleven primers by clustering via principal component analysis (PCA) and multivariate heatmap biostatistical methods differentiated the two Egyptian cultivars EGY1-Ismailia1 and EGY2-Nubaria1 from the three Australian and seven American cultivars, with some distinction of the cv. USA6-SW9720 and cv. AUS4-SuperFast. The results were also supported by the sequence analysis of the matK and the trnH genes on the genetic relatedness between eight cultivars. Moreover, it might be suggested that breeding lines from M. sativa cultivars may provide novel insights and a better understanding of the domestication of M. sativa genetic diversity. The classification of the eight cultivars, as revealed by morpho-agronomic traits, confirmed the close genetic relationship between the two Egyptian cultivars and indicated some resemblance between them and the AUS2-Siri Nafa, whereas the two American cultivars, USA1-Super supreme and USA4-Cuf101, were clearly isolated from a cluster of other three cultivars USA7-SW9628, USA8-Magna901, and USA9-Perfect. The results are useful sources of genetic information for future breeding programs in crop development and open new possibilities of producing M. sativa lines harboring high forage quality, productivity, and resistance to biotic and abiotic stresses.

Multicomponent synthesis of substituted and fused-ring imidazoles via phospha-münchnone cycloaddition.

A new, one-pot synthesis of imidazoles from imines, acid chlorides, and N-nosyl imines or tethered nitriles is reported. The reaction is mediated by the phosphonite PPh(catechyl) and proceeds via regioselective cycloaddition with an in situ-generated phospha-münchnone 1,3-dipole. This provides an efficient route to construct both highly substituted and polycyclic imidazoles directly from available substrates, without metal catalysts, and with access to product diversity.

Phosphonite mediated 1,3-dipolar cycloaddition: a route to polycyclic 2-pyrrolines from imines, acid chlorides and alkenes.

2-Pyrrolines can be generated by the PhP(2-catechyl) mediated coupling of alkene-tethered imines and acid chlorides. This reaction proceeds via phosphorus-containing 1,3-dipoles, which undergo cycloaddition with alkenes with high stereo- and regioselectivity. The modularity of this reaction can be used to assemble a range of polysubstituted pyrrolines in one pot transformations.

Rhodium-catalyzed enantioselective addition of boronic acids to N-benzylnicotinate salts.

The highly enantioselective catalytic asymmetric addition of aryl and alkenylboronic acids to N-benzylnicotinate salt 1 is described. The dihydropyridine 2 reaction products can be converted to synthetically useful piperidines. Application of the methodology to the preparation of enantioenriched quaternary chiral centers is also discussed.