Combined Nanofibrous Face Mask: Co-Formulation of Lipases and Antibiotic Agent by Electrospinning Technique

The application of enzyme-based therapies has received significant attention in modern drug development. Lipases are one of the most versatile enzymes that can be used as therapeutic agents in basic skin care and medical treatment related to excessive sebum production, acne, and inflammation. The traditional formulations available for skin treatment, such as creams, ointments or gels, are widely applied; however, their use is not always accompanied by good drug penetration properties, stability, or patient adherence. Nanoformulated drugs offer the possibility of combining enzymatic and small molecule formulations, making them a new and exciting alternative in this field. In this study polymeric nanofibrous matrices made of polyvinylpyrrolidone and polylactic acid were developed, entrapping lipases from Candida rugosa and Rizomucor miehei and antibiotic compound nadifloxacin. The effect of the type of polymers and lipases were investigated, and the nanofiber formation process was optimized to provide a promising alternative in topical treatment. Our experiments have shown that entrapment by electrospinning induced two orders of magnitude increase in the specific enzyme activity of lipases. Permeability investigations indicated that all lipase-loaded nanofibrous masks were capable of delivering nadifloxacin to the human epidermis, confirming the viability of electrospinning as a formulation method for topical skin medications

Endothelial cell activation is attenuated by everolimus via transcriptional and post-transcriptional regulatory mechanisms after drug-eluting coronary stenting.

We previously found higher level of endothelial cell (EC) activation in patients who suffered from in-stent restenosis after bare-metal stenting compared to subjects who underwent drug-eluting stenting (DES) showing no complications. Here we investigated the potential transcriptional and post-transcriptional regulatory mechanisms by which everolimus attenuated EC activation after DES. We studied the effect of everolimus on E-selectin (SELE) and VCAM1 mRNA levels when human coronary artery (HCAECs) and human umbilical vein ECs were challenged with recombinant TNF-alpha (100 ng/mL) for 1-24 hours in the presence or absence of everolimus using 0.5 muM concentration locally maintained by DES. EC activation was evaluated via the levels of IL-1beta and IL-6 mRNAs with miR-155 expression by RT-qPCR as well as the nuclear translocation of nuclear factor kappa beta (NF-kappaB) detected by fluorescence microscopy. To investigate the transcriptional regulation of E-selectin and VCAM-1, TNF-alpha-induced enhancer RNA (eRNA) expression at p65-bound enhancers in the neighboring genomic regions of SELE and VCAM1 genes, including SELE_-11Kb and VCAM1_-10Kb, were measured in HCAECs. Mature and precursor levels of E-selectin and VCAM-1 repressor miR-181b were quantified to analyze the post-transcriptional regulation of these genes in HCAECs. Circulating miR-181b was analyzed in plasma samples of stented subjects by stem-loop RT-qPCR. TNF-alpha highly elevated E-selectin and VCAM-1 expression at transcriptional level in ECs. Levels of mature, pre- and pri-miR-181b were repressed in ECs by TNF-alpha, while everolimus acted as a negative regulator of EC activation via inhibited translocation of NF-kappaB p65 subunit into cell nuclei, lowered eRNA expression at SELE and VCAM1 genes-associated enhancers and modulated expression of their post-transcriptional repressor miR-181b. Significant negative correlation was observed between plasma miR-181b and soluble E-selectin and VCAM-1 in patients. In conclusion, everolimus attenuates EC activation via reduced NF-kappaB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES

Synthesis, experimental and theoretical studies on the factors influencing the pKa values of new crown ethers containing a diarylphosphinic acid unit

Abstract Synthesis of acidic new crown ethers containing a diarylphosphinic acid unit has been accomplished. The aromatic rings of the crown ethers were substituted with tert-butyl and nitro groups. Nitro substitution of the crown ethers was investigated. pKa determination of the new proton-ionizable crown ethers has been performed, showing the effect of the substituents of the aromatic rings on the acidity. An anomaly was discovered in the pKa values and an explanation was given based on quantum mechanical calculations and molecular dynamics simulations

Increased Short-Term Beat-to-Beat QT Interval Variability in Patients with Impaired Glucose Tolerance

Prediabetic states and diabetes are important risk factors for cardiovascular morbidity and mortality. Determination of short-term QT interval variability (STVQT) is a non-invasive method for assessment of proarrhythmic risk. The aim of the study was to evaluate the STVQT in patients with impaired glucose tolerance (IGT). 18 IGT patients [age: 63 +/- 11 years, body mass index (BMI): 31 +/- 6 kg/m2, fasting glucose: 6.0 +/- 0.4 mmol/l, 120 min postload glucose: 9.0 +/- 1.0 mmol/l, hemoglobin A1c (HbA1c): 5.9 +/- 0.4%; mean +/- SD] and 18 healthy controls (age: 56 +/- 9 years, BMI: 27 +/- 5 kg/m2, fasting glucose: 5.2 +/- 0.4 mmol/l, 120 min postload glucose: 5.5 +/- 1.3 mmol/l, HbA1c: 5.4 +/- 0.3%) were enrolled into the study. ECGs were recorded, processed, and analyzed off-line. The RR and QT intervals were expressed as the average of 30 consecutive beats, the temporal instability of beat-to-beat repolarization was characterized by calculating STVQT as follows: STVQT = Sigma|QTn + 1 - QTn| (30x radical2)-1. Autonomic function was assessed by means of standard cardiovascular reflex tests. There were no differences between IGT and control groups in QT (411 +/- 43 vs 402 +/- 39 ms) and QTc (431 +/- 25 vs 424 +/- 19 ms) intervals or QT dispersion (44 +/- 13 vs 42 +/- 17 ms). However, STVQT was significantly higher in IGT patients (5.0 +/- 0.7 vs 3.7 +/- 0.7, P < 0.0001). The elevated temporal STVQT in patients with IGT may be an early indicator of increased instability of cardiac repolarization during prediabetic conditions