pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer

Background Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown. Results Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells. Conclusions These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment. Graphic Abstarct

Albumin-binding Aptamer Chimeras for Improved siRNA Bioavailability

Short interfering RNAs (siRNAs) are potent nucleic acid-based drugs designed to target disease driving genes that may otherwise be undruggable with small molecules. However, the potential of administering therapeutic siRNA in vivo is limited by poor pharmacokinetic properties, including rapid renal clearance and nuclease degradation. Nanocarriers have traditionally been explored as means to overcome these challenges, but they have intrinsic downsides such as dose-limiting toxicity and synthetic complexity. Backpacking on natural carriers such as albumin, which is present at high concentration and has a long half-life in serum, is an effective way to modify pharmacokinetics of biologic drugs that otherwise have poor bioavailability. In this work, we sought to develop albumin-binding aptamer-siRNA chimeras to improve the bioavailability of siRNA. We used a Systematic Evolution of Ligands through Exponential Enrichment (SELEX) approach to obtain RNA aptamers with modified bases that bind albumin with high affinity. We then fused the aptamers directly to an siRNA to generate the chimera structure. These aptamer-siRNA chimeras are stable in serum, exhibit potent gene knockdown capabilities in vitro, and display extended circulation time in vivo. We suggest that this albumin-binding aptamer-siRNA chimera approach is a promising strategy for drug delivery applications.

Endogenous Enzyme-responsive Nanoplatforms for Anti-tumor Therapy

: The emergency of responsive drug delivery systems has contributed to the reduced cytotoxicity, the improved permeability in tissues and extended circulation time of the active drug. Of particular, enzyme-responsive nanoplatforms have attracted a lot due to the specificity and efficiency of an enzyme-catalyzed reaction. In this review, enzyme-based mono responsive drug delivery systems designed in the past 5 years were summarized. These drug delivery systems were introduced by different tumor-related enzymes such as matrix metalloproteinase, esterase, hyaluronidase, caspase and cathepsin. Moreover, the enzyme-sensitive nanoplatforms activated by dual-stimuli were also described. Although great progress had been made in the past years, the translation into clinical practice was still difficult. Thus, three obstacles (enzyme heterogeneity, reaction environment, animal model) were also discussed. In short, enzymeactivated drug delivery systems offer great potential in treating cancers.

Creating modern competitive hybrids tomato for greenhouse plants of small-volume hydroponics

Study was carried out for new heterotic tomato hybrids at a modern greenhouse complex JSC “Teplichnoye” in 2016-2018, which located in the village of Sadovy, urban okryga Verkhnyaya Pyshma, Sverdlovsk region. Hybrids were included in the experimental scheme 901, 950, 951, 1001, 12000, 12002, 12283, 12294, 12898, 12899, it was selected Holland-select “Romano” hybrid as a control for the study. Plants were studied in extended circulation of winter greenhouses in small-volume hydroponics. It was found that in the newly studied hybrids 901, 950, 951, and 12283, flowering and fruiting occurred a week earlier in comparison with the control and other variants. The most productive were hybrids 951, 901, 12283, 12899, the yields of which exceeded the control 10.5-29.2 kg. The most productive hybrid 951-78.6 kg / m2. Due to the high individual yield, the level of profitability of the above hybrids was the highest, therefore hybrids 901, 951, 12283, 12899 can be recommended for cultivation in extended circulation of winter greenhouses of small-volume technology.

Construction of Biodegradable Core Cross-Linked Nanoparticles from Near Infrared Dyes Encoded Polyprodrug Amphiphiles and Synergistic Anticancer Investigation

It has been widely accepted that covalently framed nanoparticles showed extended circulation time in the blood due to their large stable structures compared to the free linear polyprodrugs. Herein, an...

Chemical and isotopic composition of nitrogen thermal waters of the Kuldur Deposit (JAR, Russia)

The article presents the results of the hydrogeochemical study of thermal groundwaters from the Kuldur spa (Jewish Autonomous Region, Russia). The main characteristics of these groundwaters are high temperature (73 ᵒС), low TDS (up to 0,38 g/l), and alkaline (pH 9). The dominated cation is sodium, and the anion is hydrocarbonate. Water is enriched with fluorine, silicon, aluminum, tungsten, molybdenum, and some other anionic elements. This study provides detailed data on the chemical and mineral composition of host rocks and sources of solutes. Isotopic data from bubbling gases show that the main component of the gas phase (N2) comes from an atmogenic source, while CH4 and CO2 are biogenic. Argon and oxygen are also derived from air, while helium is predominantly radiogenic. The ϬD and Ϭ18О in the aqueous phase indicate the undoubtedly meteoric genesis of groundwater with an extended circulation period. Our results suggest that the studied groundwaters are results of the penetration of meteoric waters to 4 km depth and heating up to 100 ᵒC. The solutes come to aquifer via the dissolution of rocks, but since groundwater circulates within the poorly soluble rock (granitoids), respectively, the water TDS remains low.

Transformation of social housing kitchens over time: Nicosia Göçmenköy social houses as a case study

PurposeIn this study, it was aimed to determine the changes made by users in kitchens of social housing units of Nicosia Göçmenköy and to determine the user satisfaction with a questionnaire survey.Design/methodology/approachThis study was carried out in two stages. In the first stage, the renovations in the residential kitchens were determined by on-site observation. Revisions in the kitchens compared to the standard kitchen are expressed by drawings. In the second stage, 49 people who lived in these dwellings and accepted to participate were asked questions to determine the satisfaction levels of the users of existing kitchens through a questionnaire.FindingsAs a result of on-site observations, it was seen that changes and enlargements in kitchen spaces did not add value to the spaces in terms of function in many examples, but rather they made a negative impact on the kitchen activities. It is also a fact that random and optional additions and enlargements cause the creation of architecturally useless areas and extended circulation areas instead of the expected benefits. According to the results of the questionnaire survey, it was determined that the users of the kitchens who renovated their kitchens were very satisfied with the current kitchens.Originality/valueWhen the recent studies in world literature are examined, it can be seen that research on kitchen spaces is not so much. There is no detailed study on the transformation of social housing kitchens in Cyprus so far. This study aims to determine the transformations in Göçmenköy social housing kitchens, which are the first social residences built by the state in the Nicosia Göçmenköy region. Since the studies on social housing kitchens are very limited, this study is very valuable in terms of shedding light on future researches.

Real-time particle-by-particle detection of erythrocyte-camouflaged microsensor with extended circulation time in the bloodstream

Personalized medicine offers great potential benefits for disease management but requires continuous monitoring of drugs and drug targets. For instance, the therapeutic window for lithium therapy of bipolar disorder is very narrow, and more frequent monitoring of sodium levels could avoid toxicity. In this work, we developed and validated a platform for long-term, continuous monitoring of systemic analyte concentrations in vivo. First, we developed sodium microsensors that circulate directly in the bloodstream. We used “red blood cell mimicry” to achieve long sensor circulation times of up to 2 wk, while being stable, reversible, and sensitive to sodium over physiologically relevant concentration ranges. Second, we developed an external optical reader to detect and quantify the fluorescence activity of the sensors directly in circulation without having to draw blood samples and correlate the measurement with a phantom calibration curve to measure in vivo sodium. The reader design is inherently scalable to larger limbs, species, and potentially even humans. In combination, this platform represents a paradigm for in vivo drug monitoring that we anticipate will have many applications in the future.

Aza-crown ether locked on polyethyleneimine: solving the contradiction between transfection efficiency and safety during in vivo gene delivery

An aza-crown ether derivative to lock a hyperbranched PEI, which endows the PEI with tumor targeting ability, antiserum ability and extended circulation in the blood, meanwhile retaining the high gene complexation and high transfection efficiency.

Testing of tomato hybrids of the breeding of the company "Gavrish" in JSC "Teplichnoye" of the Tambov region

Relevance Currently, the requirements for modern tomato hybrids are increasing both from consumers and from producers. Modern tomato hybrids in extended circulation should yield at least 60 kg / m2, be distinguished by high quality of fruits, early ripeness, possess manufacturability, resistance to major diseases. Along with the traditional form of fruits, hybrids with original shape, color, taste and aroma are interesting for manufacturers. Methods The aim of the research was the variety study of indeterminant F1 hybrids of tomato breeding of the company "Gavrish" in JSC "Teplichnoye" of the Tambov region. Studies were conducted in 2017-2018 in the extended and summer-autumn turnover in the conditions of JSC "Teplichnoye" of the Tambov region in accordance with generally accepted recommendations for research with vegetable crops in greenhouses. The objects of the study in extended circulation were tomato hybrids: F1 Bao Bab, F1 Baloven, the F1 Torero hybrid was taken as a control. In the summerautumn turnover, a study was made of the rose hybrid – F1 Panthera; the Rosario F1 hybrid was used as a control; a hybrid with a plum-shaped fruit – F1 Armata, control – a hybrid F1 Lezghinka. Results According to the results of the study of tomato hybrids, the selection of the Gavrish company at the enterprise made the decision to grow it in extended circulation and increase the area under F1 Baloven, in the summer-autumn turnover under the F1 Panthera hybrid.