Activity

Consequently, the synthesized RAOA displayed good amphiphilic properties with a critical aggregation concentration (CAC) of 0.43 g/L in NaCl solution, which was significantly lower than that of SA, and formed regular self-assembled micelles with an average hydrodynamic diameter of 277 nm (PDI = 0.19) and a zeta potential of about -69.8 mV. Meanwhile, the drug-loaded RAOA microcapsules had a relatively high encapsulation efficiency (EE) of 87.6 % and good sustained-release properties in comparison to the drug-loaded SA aggregates, indicating the good affinity of RAOA to hydrophobic ibuprofen. The swelling and degradation of RAOA microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Moreover, it also displayed low cytotoxicity against the RAW264.7 cell, similar to the SA aggregates. In view of the excellent advantages of RAOA, it is expected to become the ideal candidate for hydrophobic drug delivery in the biomedical field.A simple and fast method for the analysis of lactate from a single drop of blood was developed. The finger-prick whole blood sample (10 µL) was diluted (120) with a 7% (w/v) solution of propanesulfonic acid and applied to a blood plasma separation device. The device accommodates a membrane sandwich composed of an asymmetric polysulfone membrane and a supporting textile membrane that allows the collection of blood plasma into a narrow glass capillary in less than 20 s. Separated and simultaneously diluted blood plasma was directly injected into a capillary electrophoresis instrument with a contactless conductivity detector (CE-C4D) and analyzed in less than one minute. A separation electrolyte consisted of 10 mmol/L l-histidine, 15 mmol/L dl-glutamic acid, and 30 µmol/L cetyltrimethylammonium bromide. The whole procedure starting from the finger-prick sampling until the CE-C4D analysis was finished, took less than 5 min and was suitable for monitoring lactate increase in blood plasma during incremental cycling exercise. The observed lactate increase during the experiments measured by the developed CE-C4D method correlated well with the results from a hand-held lactate analyzer (R = 0.9882). The advantage of the developed CE method is the speed, significant savings per analysis, and the possibility to analyze other compounds from blood plasma.Gui Zhen Cao is an herbal formulation that has been documented in Chinese traditional medicine as a remedy for diarrhea, dysentery, inflammation, and toxicity. The sources of this formulation (Bidens pilosa L., Bidens biternata (Lour.) Merr. & Sherff, Bidens bipinnata L.) are also listed in ethnomedicinal reports all over the world. In this study, all these plants are tested for in vitro anticandida activity. A quantitative evaluation of the phytochemicals in all these plants indicated that their vegetative parts are rich in tannins, saponins, oxalates, cyanogenic glycoside and lipids; moreover, the roots have high percentages of alkaloids, flavonoids, and phenols. The results indicated significant anticandida activity, especially for the hexane extract of B. bipinnata leaves which inhibited C. albicans (42.54%), C. glabrata (46.98%), C. tropicalis (50.89%), C. krusei (40.56%), and C. orthopsilosis (50.24%). The extract was subjected to silica gel chromatography and 220 fractions were obtained. Purification by High Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) and Gas Chromatography tandem Mass Spectrometry (GC-MS/MS) analysis led to the identification of two anticandida compounds dehydroabietic and linoleic acid having an inhibition of 85 and 92%, respectively.In this work, we designed, developed, characterized, and investigated a new chelator and its bifunctional derivative for 89Zr labeling and PET-imaging. In a preliminary study, we synthesized two hexadentate chelators named AAZTHAS and AAZTHAG, based on the seven-membered heterocycle AMPED (6-amino-6-methylperhydro-1,4-diazepine) with the aim to increase the rigidity of the 89Zr complex by using N-methyl-N-(hydroxy)succinamide or N-methyl-N-(hydroxy)glutaramide pendant arms attached to the cyclic structure. N-methylhydroxamate groups are the donor groups chosen to efficiently coordinate 89Zr. After in vitro stability tests, we selected the chelator with longer arms, AAZTHAG, as the best complexing agent for 89Zr presenting a stability of 86.4 ± 5.5% in human serum (HS) for at least 72 h. Small animal PET/CT static scans acquired at different time points (up to 24 h) and ex vivo organ distribution studies were then carried out in healthy nude mice (n = 3) to investigate the stability and biodistribution in vivo of this new 89Zr-based complex. High stability in vivo, with low accumulation of free 89Zr in bones and kidneys, was measured. Furthermore, an activated ester functionalized version of AAZTHAG was synthesized to allow the conjugation with biomolecules such as antibodies. The bifunctional chelator was then conjugated to the human anti-HER2 monoclonal antibody Trastuzumab (Tz) as a proof of principle test of conjugation to biologically active molecules. The final 89Zr labeled compound was characterized via radio-HPLC and SDS-PAGE followed by autoradiography, and its stability in different solutions was assessed for at least 4 days.Prunus mume blossom is an edible flower that has been used in traditional Chinese medicine for thousands of years. Flavonoids are one of the most active substances in Prunus mume blossoms. The optimal ultrasonic-assisted enzymatic extraction of flavonoids from Prunus mume blossom (FPMB), the components of FPMB, and its protective effect on injured cardiomyocytes were investigated in this study. According to our results, the optimal extraction process for FPMB is as follows cellulase at 2.0%, ultrasonic power at 300 W, ultrasonic enzymolysis for 30 min, and an enzymolysis temperature of 40 °C. FPMB significantly promoted the survival rate of cardiomyocytes and reduced the concentration of reactive oxygen species (ROS). FPMB also improved the activities of proteases caspase-3, caspase-8, and caspase-9 in cardiomyocytes. The cardiomyocyte apoptosis rate in mice was significantly reduced by exposure to FPMB. These results suggest that the extraction rate of FPMB may be improved by an ultrasonic-assisted enzymatic method. FPMB has a protective effect on the injured cardiomyocytes.Despite the significant relevance of photodynamic therapy (PDT) as an efficient strategy for primary and adjuvant anticancer treatment, several challenges compromise its efficiency. In order to develop an “ideal photosensitizer” and the requirements applied to photosensitizers for PDT, there is still a need for new photodynamic agents with improved photophysical and photobiological properties. In this study, we performed a detailed characterization of two tetracyanotetra(aryl)porphyrazine dyes with 4-biphenyl (pz II) and 4-diethylaminophenyl (pz IV) groups in the periphery of the porphyrazine macrocycle. Photophysical properties, namely, fluorescence quantum yield and lifetime of both photosensitizers, demonstrate extremely high dependence on the viscosity of the environment, which enables them to be used as viscosity sensors. PzII and pz IV easily enter cancer cells and efficiently induce cell death under light irradiation. Using fluorescence lifetime imaging microscopy, we demonstrated the possibility of assessing local intracellular viscosity and visualizing viscosity changes driven by PDT treatment with the compounds. Thus, pz II and pz IV combine the features of potent photodynamic agents and viscosity sensors. These data suggest that the unique properties of the compounds provide a tool for PDT dosimetry and tailoring the PDT treatment regimen to the individual characteristics of each patient.The increasing incidence of antifungal resistance represents a great challenge in the medical area and, for this reason, new therapeutic alternatives for the treatment of fungal infections are urgently required. Cold atmospheric plasma (CAP) has been proposed as a promising alternative technique for the treatment of superficial candidiasis, with inhibitory effect both in vitro and in vivo. However, little is known on the association of CAP with conventional antifungals. The aim of this study was to evaluate the effects of the association between CAP and conventional polyene antifungals on Candida albicans biofilms. C. albicans SC 5314 and a clinical isolate were used to grow 24 or 48 h biofilms, under standardized conditions. After that, the biofilms were exposed to nystatin, amphotericin B and CAP, separately or in combination. Different concentrations of the antifungals and sequences of treatment were evaluated to establish the most effective protocol. Biofilms viability after the treatments was compared to negative control. Data were compared by One-way ANOVA and post hoc Tukey (5%). The results demonstrate that 5 min exposure to CAP showed more effective antifungal effect on biofilms when compared to nystatin and amphotericin B. Additionally, it was detected that CAP showed similar (but smaller in magnitude) effects when applied in association with nystatin and amphotericin B at 40 µg/mL and 60 µg/mL. Therefore, it can be concluded that the application of CAP alone was more effective against C. albicans biofilms than in combination with conventional polyene antifungal agents.Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes and a pro-inflammatory milieu in the skin. While patients with moderate to severe psoriasis are treated using targeted therapies (small molecules and monoclonal antibodies), patients suffering from milder forms are still in need of effective topical products without adverse effects. Antimony compounds (ACs) are regularly used as anti-inflammatory compounds in traditional and anthroposophic medicine and as antiprotozoan drugs. Here, we examined the effect of metallic antimony, natural antimony(III) sulfide and potassium antimonyl(III) tartrate in vitro on psoriasis-like keratinocytes and the human dendritic cell line THP-1 using qPCR, immunocytochemistry, ELISA and flow cytometry. In psoriatic keratinocytes, ACs inhibited the overexpression of the antimicrobial peptide β-defensin 2 and glucose transporter 1, as well as the hyperproliferation marker keratin 17. Furthermore, ACs mediated anti-inflammatory effects by reducing nuclear translocation of the p65 subunit of NF-κB and pSTAT3 and inhibited pro-inflammatory cytokine secretion by keratinocytes. In addition, ACs displayed anti-psoriatic effects by reducing the activation of IFN-α-treated THP-1 cells as well as the expression of the psoriasis-promoting master cytokine IL-23 by these cells. While all ACs showed anti-psoriatic effects, the most prominent results were seen with potassium antimonyl(III) tartrate. Selleck 1-PHENYL-2-THIOUREA In summary, ACs display numerous anti-psoriatic effects in vitro at subtoxic concentrations. We conclude that ACs are interesting compounds for the topical treatment of psoriasis that warrant further investigation in clinical studies.We report the development of in vitro propagation protocols through an adventitious shoot induction pathway for a rare and medicinal Scutellaria havanensis. In vitro propagation studies using nodal explants showed MS medium supplemented with 10 µM 6-Benzylaminopurine induced the highest number of adventitious shoots in a time-dependent manner. A ten-day incubation was optimum for shoot bud induction as longer exposures resulted in hyperhydricity of the explants and shoots induced. We also report preliminary evidence of Agrobacterium tumefaciens EHA105-mediated gene transfer transiently expressing the green fluorescent protein in this species. Transformation studies exhibited amenability of various explant tissues, internode being the most receptive. As the plant has medicinal value, research was carried out to evaluate its potential antioxidant capacity and the efficacy of methanolic leaf extracts in curbing the viability of human colorectal cancer cell line HCT116. Comparative total polyphenol and flavonoid content measurement of fresh and air-dried leaf extract revealed that the fresh leaf extracts contain higher total polyphenol and flavonoid content.