Abstract d -α-tocopheryl polyethylene glycol succinate (Vitamin E TPGS, or simply TPGS) is a water-soluble derivative of natural Vitamin E, which is formed by esterification of Vitamin E succinate ...with polyethylene glycol (PEG). As such, it has advantages of PEG and Vitamin E in application of various nanocarriers for drug delivery, including extending the half-life of the drug in plasma and enhancing the cellular uptake of the drug. TPGS has an amphiphilic structure of lipophilic alkyl tail and hydrophilic polar head with a hydrophile/lipophile balance (HLB) value of 13.2 and a relatively low critical micelle concentration (CMC) of 0.02% w/w, which make it to be an ideal molecular biomaterial in developing various drug delivery systems, including prodrugs, micelles, liposomes and nanoparticles, which would be able to realize sustained, controlled and targeted drug delivery as well as to overcome multidrug resistance (MDR) and to promote oral drug delivery as an inhibitor of P-glycoprotein (P-gp). In this review, we briefly discuss its physicochemical and pharmaceutical properties and its wide applications in composition of the various nanocarriers for drug delivery, which we call TPGS-based drug delivery systems.
Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been ...initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and the number of newly generated cardiomyocytes and vascular cells, either by transdifferentiation or cell fusion, appear too low to explain the significant cardiac improvement described. Accordingly, we and others have advanced an alternative hypothesis: the transplanted stem cells release soluble factors that, acting in a paracrine fashion, contribute to cardiac repair and regeneration. Indeed, cytokines and growth factors can induce cytoprotection and neovascularization. It has also been postulated that paracrine factors may mediate endogenous regeneration via activation of resident cardiac stem cells. Furthermore, cardiac remodeling, contractility, and metabolism may also be influenced in a paracrine fashion. This article reviews the potential paracrine mechanisms involved in adult stem cell signaling and therapy.
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•BSFP shows excellent chemical and thermal compatibilities with GDC electrolyte.•The polarization resistance (Rp) of the cathode is 0.18 Ω cm2 at 700 °C.•Oxygen reduction reaction ...mechanism is studied.•The peak power density of the single cell is 0.56 W cm−2 at 700 °C.
High catalytic activity of cathode material is one of the key requirements for the practical application of solid oxide fuel cells (SOFC). Here we designed and evaluated a novel non-metal P-doped (Bi, Sr)FeO3−δ, i.e., Bi0.5Sr0.5Fe0.95P0.05O3−δ (BSFP) oxide, as cathode material. BSFP with a cubic structure presents excellent chemical compatibility with Ce0.9Gd0.1O1.95 (GDC) electrolyte after sintering at 1100 °C. Impedance analysis reveals its polarization resistance (Rp) is as low as 0.18 Ω cm2 at 700 °C. Further kinetics study suggests the low-frequency process is the rate-limiting step of the oxygen reduction reaction (ORR). An anode-supported single cell delivers attractive power output of 0.56 W cm−2 at 700 °C. The electroactivity is superior to undoped (Bi, Sr)FeO3−δ, indicating that BSFP perovskite could be a promising cathode for SOFC operating at intermediate temperatures.
The East Asian summer monsoon (EASM) northern boundary is a critical indicator of EASM variations. Movement of the boundary is modulated by both the EASM and the mid-latitude westerlies. Here, we use ...the Earth system model EC-Earth to quantify the contribution of orbital forcing and vegetation feedbacks in modulating the movement of EASM northern boundary. The results show that the simulated EASM northern boundary during the mid-Holocene shifts by a maximum of ∼213 km northwestward due to orbital forcing. When the model was coupled with a dynamic vegetation module LPJ-GUESS, the northern boundary shifts further northwestward by a maximum of ∼90 km, indicating the importance of vegetation feedbacks.
During the mid-Holocene, temperature increased in the mid-latitude during the boreal summer due to insolation, leading to increased meridional air temperature differences (MTDs) over the region north of 45°N and to decreased MTDs to the south. The changes in the temperature gradient weakened the East Asian Westly Jet (EAWJ) and displaced it northward, resulting in an earlier transition of the Meiyu stage and a more prolonged Midsummer stage. The northward movement of EAWJ, combined with the enhanced southerly moisture flow from South China, caused more precipitation in North China and eventually to a northwestward shift of the northern boundary of the EASM. The coupled dynamic vegetation module LPJ-GUESS simulated more grassland and less forest over Northeast Asia during the mid-Holocene. The increased surface albedo tended to lower the temperature in the region, and further enhanced the MTDs in mid-latitude East Asia, leading to the further northward movement of the EAWJ and a northwestward shift of the EASM northern boundary. Although the simulated vegetation distribution in several regions may be not accurate, it reflects the substantial contribution of climate-vegetation interaction on modulating the EASM.
•The maximum northwestward extension was ∼213 km due to orbital forcing, and a maximum of ∼90 km due to vegetation feedbacks..•The changes of the EAWJ contributed to the shift of the EASM northern boundary during the mid-Holocene.•The dynamic vegetation module LPJ-GUESS simulated more grassland and less forest over Northeast Asia.
The capacity of lipid and carotenoid production by Rhodotorula glutinis was investigated under different irradiation conditions, temperatures and C/N ratios. The results showed that ...dark/low-temperature could enhance lipid content, while irradiation/high-temperature increased the yields of biomass and carotenoid. The optimum C/N ratio for production was between 80 and 100. A two-stage cultivation strategy was used for lipid and carotenoid production in a 5L fermenter. In the first stage, the maximum biomass reached 28.1g/L under irradiation/high-temperature. Then, the cultivation condition was changed to dark/low-temperature, and C/N ratio was adjusted to 90. After the second stage, the biomass, lipid content and carotenoid reached 86.2g/L, 26.7% and 4.2mg/L, respectively. More significantly, the yields of biomass and lipid were 43.1% and 11.5%, respectively. Lipids contained 79.7% 18C and 16.8% 16C fatty acids by GC analysis. HPLC quantified the main carotenoids were β-carotene (68.4%), torularhodin (21.5%) and torulene (10.1%).
Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug ...carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015–2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.
This review makes a concise overview of current progress in the research of drug delivery systems that focused on the delivery strategies, construction techniques and specific representatives. Display omitted
Uncoating is an obligatory step in the virus life cycle that serves as an antiviral target. Unfortunately, it is challenging to study viral uncoating due to methodology limitations for detecting this ...transient and dynamic event. The uncoating of influenza A virus (IAV), which contains an unusual genome of eight segmented RNAs, is particularly poorly understood. Here, by encapsulating quantum dot (QD)-conjugated viral ribonucleoprotein complexes (vRNPs) within infectious IAV virions and applying single-particle imaging, we tracked the uncoating process of individual IAV virions. Approximately 30% of IAV particles were found to undergo uncoating through fusion with late endosomes in the “around-nucleus” region at 30 to 90 minutes postinfection. Inhibition of viral M2 proton channels and cellular endosome acidification prevented IAV uncoating. IAV vRNPs are released separately into the cytosol after virus uncoating. Then, individual vRNPs undergo a three-stage movement to the cell nucleus and display two diffusion patterns when inside the nucleus. These findings reveal IAV uncoating and vRNP trafficking mechanisms, filling a critical gap in knowledge about influenza viral infection.
Cancer immunotherapy is mainly focused on manipulating patient's own immune system to recognize and destroy cancer cells. Vaccine formulations based on nanotechnology have been developed to target ...delivery antigens to antigen presenting cells (APCs), especially dendritic cells (DCs) for efficiently induction of antigen-specific T cells response. To enhance DC targeting and antigen presenting efficiency, we developed erythrocyte membrane-enveloped poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for antigenic peptide (hgp10025-33) and toll-like receptor 4 agonist, monophosphoryl lipid (MPLA). A Mannose-inserted membrane structure was constructed to actively target APCs in the lymphatic organ, and redox-sensitive peptide-conjugated PLGA nanoparticles were fabricated which prone to cleave in the intracellular milieu. The nanovaccine demonstrated the retained protein content in erythrocyte and enhanced in vitro cell uptake. An antigen-depot effect was observed in the administration site with promoted retention in draining lymph nodes. Compared with other formulations after intradermal injection, the nanovaccine prolonged tumor-occurring time, inhibited tumor growth, and suppressed tumor metastasis in prophylactic, therapeutic, and metastatic melanoma models, respectively. Additionally, we revealed that nanovaccine effectively enhanced IFN-γ secretion and CD8(+) T cell response. Taken together, these results demonstrated the great potential in applying an erythrocyte membrane-enveloped polymeric nanoplatform for an antigen delivery system in cancer immunotherapy.
Repopulation of the injured heart with new, functional cardiomyocytes remains a daunting challenge for cardiac regenerative medicine. An ideal therapeutic approach would involve an effective method ...at achieving direct conversion of injured areas to functional tissue in situ.
The aim of this study was to develop a strategy that identified and evaluated the potential of specific micro (mi)RNAs capable of inducing reprogramming of cardiac fibroblasts directly to cardiomyocytes in vitro and in vivo.
Using a combinatorial strategy, we identified a combination of miRNAs 1, 133, 208, and 499 capable of inducing direct cellular reprogramming of fibroblasts to cardiomyocyte-like cells in vitro. Detailed studies of the reprogrammed cells demonstrated that a single transient transfection of the miRNAs can direct a switch in cell fate as documented by expression of mature cardiomyocyte markers, sarcomeric organization, and exhibition of spontaneous calcium flux characteristic of a cardiomyocyte-like phenotype. Interestingly, we also found that miRNA-mediated reprogramming was enhanced 10-fold on JAK inhibitor I treatment. Importantly, administration of miRNAs into ischemic mouse myocardium resulted in evidence of direct conversion of cardiac fibroblasts to cardiomyocytes in situ. Genetic tracing analysis using Fsp1Cre-traced fibroblasts from both cardiac and noncardiac cell sources strongly suggests that induced cells are most likely of fibroblastic origin.
The findings from this study provide proof-of-concept that miRNAs have the capability of directly converting fibroblasts to a cardiomyocyte-like phenotype in vitro. Also of significance is that this is the first report of direct cardiac reprogramming in vivo. Our approach may have broad and important implications for therapeutic tissue regeneration in general.
Oral chemotherapy is an important topic in the 21st century medicine, which may radically change the current regimen of chemotherapy and greatly improve the quality of life of the patients. ...Unfortunately, most anticancer drugs, especially those of high therapeutic efficacy such as paclitaxel and docetaxel, are not orally bioavailable due to the gastrointestinal (GI) drug barrier. The molecular basis of the GI barrier has been found mainly due to the multidrug efflux proteins, i.e. P-type glycoproteins (P-gp), which are rich in the epithelial cell membranes in the GI tract. Medical solution for oral chemotherapy is to apply P-gp inhibitors such as cyclosporine A, which, however, suppress the body's immune system either, thus causing medical complication. Pharmaceutical nanotechnology, which is to apply and further develop nanotechnology to solve the problems in drug delivery, may provide a better solution and thus change the way we make drug and the way we take drug. This review is focused on the problems encountered in oral chemotherapy and the pharmaceutical nanotechnology solutions such as prodrugs, nanoemulsions, dendrimers, micelles, liposomes, solid lipid nanoparticles and nanoparticles of biodegradable polymers. Proof-of-concept in vitro and in vivo results for oral delivery of anticancer drugs by the various nanocarriers, which can be found so far from the literature, are provided.
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