Cell Survival Ratio Research Articles

Design of Cinnamaldehyde- and Gentamicin-Loaded Double-Layer Corneal Nanofiber Patches with Antibiofilm and Antimicrobial Effects.

In this study, two-layer poly(vinyl alcohol)/gelatin (PVA/GEL) nanofiber patches containing cinnamaldehyde (CA) in the first layer and gentamicin (GEN) in the second layer were produced by the electrospinning method. The morphology, chemical structures, and thermal temperatures of the produced pure (PVA/GEL), CA-loaded (PVA/GEL/CA), GEN-loaded (PVA/GEL/GEN), and combined drug-loaded (PVA/GEL/CA/GEN) nanofiber patches were determined by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and differential scanning calorimetry, respectively. Their mechanical properties, swelling and degradation behavior, and drug release kinetics were investigated. SEM images showed that both drug-free and drug-loaded nanofiber patches possess smooth and monodisperse structures, and nanofiber size increase occurred as the amount of drug increased. The tensile test results showed that the mechanical strength decreased as the drug was loaded. According to the drug release results, CA release ended at the 96th hour, while GEN release continued until the 264th hour. The antibacterial and antibiofilm activities of PVA/GEL, PVA/GEL/CA, PVA/GEL/GEN, and PVA/GEL/CA/GEN nanofiber patches against Pseudomonas aeruginosa and Staphylococcus aureus were evaluated. Results showed that PVA/GEL/GEN and PVA/GEL/CA/GEN nanofiber patches have excellent antibacterial and antibiofilm activities. Moreover, all materials were biocompatible, with no cytotoxic effects in the mammalian cell model for 8 days. PVA/GEL/GEN nanofiber patches were the most promising material for a high cell survival ratio, which was confirmed by SEM images. This research aims to develop an alternative method to stop and treat the rapid progression of bacterial keratitis.

Generation of a human haploid neural stem cell line for genome-wide genetic screening.

Haploid embryonic stem cells (haESCs) have been established in many species. Differentiated haploid cell line types in mammals are lacking due to spontaneous diploidization during differentiation that compromises lineage-specific screens. To derive human haploid neural stem cells (haNSCs) to carry out lineage-specific screens. Human haNSCs were differentiated from human extended haESCs with the help of Y27632 (ROCK signaling pathway inhibitor) and a series of cytokines to reduce diploidization. Neuronal differentiation of haNSCs was performed to examine their neural differentiation potency. Global gene expression analysis was con-ducted to compare haNSCs with diploid NSCs and haESCs. Fluorescence activated cell sorting was performed to assess the diploidization rate of extended haESCs and haNSCs. Genetic manipulation and screening were utilized to evaluate the significance of human haNSCs as genetic screening tools. Human haESCs in extended pluripotent culture medium showed more compact and smaller colonies, a higher efficiency in neural differentiation, a higher cell survival ratio and higher stability in haploidy maintenance. These characteristics effectively facilitated the derivation of human haNSCs. These human haNSCs can be generated by differentiation and maintain haploidy and multipotency to neurons and glia in the long term in vitro. After PiggyBac transfection, there were multiple insertion sites in the human haNSCs' genome, and the insertion sites were evenly spread across all chromosomes. In addition, after the cells were treated with manganese, we were able to generate a list of manganese-induced toxicity genes, demonstrating their utility as genetic screening tools. This is the first report of a generated human haploid somatic cell line with a complete genome, proliferative ability and neural differentiation potential that provides cell resources for recessive inheritance and drug targeted screening.

Preparation of Biocompatible Manganese Selenium-Based Nanoparticles with Antioxidant and Catalytic Functions.

The specificity of the tumor microenvironment (TME) severely limits the effectiveness of tumor treatment. In this study, we prepared a composite nanoparticle of manganese dioxide and selenite by a one-step redox method, and their stability under physiological conditions was improved with a bovine serum protein modification to obtain MnO2/Se-BSA nanoparticles (SMB NPs). In the SMB NPs, manganese dioxide and selenite endowed the SMB NPs with acid-responsive and catalytic, and antioxidant properties, respectively. The weak acid response, catalytic activity, and antioxidant properties of composite nanoparticles were verified experimentally. Moreover, in an in vitro hemolysis assay, different concentrations of nanoparticles were incubated with mouse erythrocytes, and the hemolysis ratio was less than 5%. In the cell safety assay, the cell survival ratio was as high as 95.97% after the co-culture with L929 cells at different concentrations for 24 h. In addition, the good biosafety of composite nanoparticles was verified at the animal level. Thus, this study helps to design high-performance and comprehensive therapeutic reagents that are responsive to the hypoxia, weak acidity, hydrogen peroxide overexpression nature of TME and overcome the limitations of TME.

Biomaterials-Based Cell Therapy for Myocardial Tissue Regeneration.

Cardiovascular diseases (CVDs) have beenthe leading cause of death worldwide during the past several decades. Cell loss is the main problem that results in cardiac dysfunction and further mortality. Cell therapy aiming to replenish the lost cells is proposed to treat CVDs especially ischemic heart diseases which lead to a big portion of cell loss. Due to the direct injection's low cell retention and survival ratio, cell therapy using biomaterials as cell carriers has attracted more and more attention because of their promotion of cell delivery and maintenance at the aiming sites. In this review, the three main factors involved in cell therapy for myocardial tissue regeneration: cell sources (somatic cells, stem cells, and engineered cells), chemical components of cell carriers (natural materials, synthetic materials, and electroactive materials), and categories of cell delivery materials (patches, microspheres, injectable hydrogels, nanofiber and microneedles, etc.) are systematically summarized. An introduction of the methods including magnetic resonance/radionuclide/photoacoustic and fluorescence imaging for tracking the behavior of transplanted cells in vivo is also included. Current challenges of biomaterials-based cell therapy and their future directions are provided to give both beginners and professionals a clear view of the development and future trends in this area.

Neural network modeling of the dynamic inactivation of probiotics during single droplet drying for improved cell viability

Dairy products containing probiotics are often dried to improve shelf life and facilitate transportation. A reliable dynamic inactivation model has long been pursued to optimize the production by maximizing probiotics' survival during drying. How to take care of the dynamic drying process experienced by the cells for precise prediction of their survival remains a challenging task. In this work, a multi-task convolutional self-attention network (CSAN) has been developed for dynamic modeling of probiotics inactivation during single droplet drying (SDD). The convolution self-attention approach together with a unique double-branch architecture allows the neural network (NN) to learn effectively from historical data and predict inactivation dynamics throughout the whole drying process. In terms of prediction accuracy, our model ( R 2 > 0.96) outperforms many other existing models ( R 2 < 0.6 in most circumstances). By resorting to this model, two optimal SDD conditions have been identified with the resultant terminal solid contents higher than 90 wt% and cell survival ratios higher than 0.65. • A dynamic inactivation model for probiotics survival prediction during drying • Effective leaning of historical data by a convolutional self-attention neural network • A double-branch architecture allows precise prediction of inactivation dynamics • Optimized conditions identified for improved cell viability and sufficient solvent removal

The structure, characterization and dual-activity of exopolysaccharide produced by Bacillus enclensis AP-4 from deep-sea sediments

In recent years, the exopolysaccharide (EPS) produced by deep-sea bacteria has attracted the interest of various researchers. In the present study, we have explored the properties and structure of a novel exopolysaccharide (called BPS) produced by Bacillus enclensis AP-4 from deep-sea sediments. The maximum yield of BPS was 4.23 ± 0.17 g L−1 in a 2216E modified medium. 1H NMR studies of the purified BPS displayed α and β-configuration sugar residues, including mannose, glucosamine, glucose, galactose, and xylose in a molar ratio of 1.00: 0.09: 0.04: 0.09: 0.07. BPS showed a molecular weight of 23,434 Da and was abundant in hydroxyl and amino residues. In addition, BPS exhibited a rod-like structure with a rough surface and was dominated by C, N, and O elements. The exopolysaccharide demonstrated remarkable thermal stability, high degradation temperature, and excellent emulsification capacity compared to most reported exopolysaccharides. Moreover, BPS displayed better quenching activities against the four radicals, which provided favorable protection for the strain. Finally, the freezing experiment investigated the cryoprotective effect of BPS on E. coli and S. aureus. BPS effectively improved the cell survival ratio and maintained the activity of Na+/K+-ATPase, which facilitates culture preservation. To the best of our knowledge, our work is the first report suggesting that marine exopolysaccharide has dual-activity. This work presents the foundation for the analysis of the structure and properties of exopolysaccharides produced by deep-sea bacteria.

Fabrication of neuroprotective silk-sericin hydrogel: potential neuronal carrier for the treatment and care of ischemic stroke

Ischemic stroke results in severe disabilities due to extensive cellular loss and the resulting impairment of brain functions. Current methods for regenerating brain tissue are ineffective. Stroke treatment requires innovative therapeutic techniques that are both safe and effective. For neuronal repair, a promising alternative is using a hydrogel-based tissue engineering technique that delivers neurotrophic cytokines and cells to injured sites. However, the limited encapsulation effectiveness, less in vivo cell survival ratio and cytokine loss make this strategy difficult to implement. We aim to design a biomaterial that can efficiently construct a matrix enriching the survival of cells and minimizing loss in vivo cytokines to overcome these constraints. We report the development of genipin conjugated sericin hydrogels (Gen-SH) with a high porous morphology and a moderate swelling rate utilizing sericin, a natural silk protein. In vitro, Gen-SH aids in the attachment and development of neurons. Our results indicate that sericin is inherently neuroprotective and neurotrophic, branching and publicizing axon extension and avoiding hypoxia-induced cell death in primary neurons. Notably, the breakdown products of Gen-SH inherit these capabilities, saving the expense of cytokines. Furthermore, we show that the Lkb1–Nuak1 pathway is required for this neurotrophic impact, whereas the Bcl-2/Bax protein ratio is necessary for the neuroprotective effect. Transplanted in vivo, Gen-SH has a high percentage of cell survival and promotes cell proliferation. Taking all this information into account, it's clear that Gen-SH can serve as a viable carrier for treatment and care for ischemic stroke healing, both in terms of delivering neuronal cells and protecting them from oxidative damage.

Exploring the integrity of cellular membrane and resistance to digestive juices of dehydrated lactic acid bacteria as influenced by drying kinetics

The survival of probiotics after spray drying is largely related to drying kinetics experienced by cells in atomized droplets. In this study, the effect of drying kinetics on the viability, integrity of cellular membrane, and digestive stability of Lactobacillus rhamnosus GG and Lactococcus lactis subsp. cremoris was quantitatively examined, using the single droplet drying technique with reconstituted skimmed milk as protectant. Distinct inactivation histories of the strains were observed at 70 °C, with droplet sizes of 1 and 2 μL and air flow velocities of 0.45 and 1 m/s. The two strains showed similar inactivation profiles under the same condition. The order of inactivation rate and the degree of damages on the cellular membrane of dehydrated cells followed the order of drying rate, which was the highest for 1 µL at 1 m/s, followed by 1 µL at 0.45 m/s and 2 µL at 1 m/s, while 2 µL at 0.45 m/s showed the slowest inactivation. For individual drying process, the percentage of live cells with intact membrane was constantly higher than cell survival ratio. Dehydrated cells showed increased viability after in situ gastric digestion for 30 min, which could be due to the resistance of milk proteins to simulated gastric fluid and the rich nutrients of the protectant. Bacterial viability declined again after subsequent in situ intestinal digestion. The findings demonstrated the sensitivity of lactic acid bacteria toward minor changes in drying kinetics. Optimizing drying kinetics may effectively increase the survival and lower the cellular injury of spray-dried probiotics.

Simultaneous removal of aromatic pollutants and nitrate at high concentrations by hypersaline denitrification:Long-term continuous experiments investigation

If we can use toxic aromatic compounds as supplementary carbon source, the simultaneous removal of nitrate (NO3−) and aromatic compounds may be achieved at much lower chemical costs. This study uses the expanded granular sludge bed (EGSB) reactors to investigate the hypersaline (> 3%) denitrification performance, the removal of aromatic compounds, i.e., aniline, phenol, and their mixture, and the mechanisms involved in. The four reactors exhibit high removal efficiency of NO3− (> 92.8%) and aromatic compounds (> 73.9%) at 0–1200 mg/L of aromatic compounds. The formation of toxic intermediates such as catechol and azo dyes is revealed by gas chromatography mass spectrometry (GC–MS) with and without N,O-Bis(trimethylsilyl) trifluoroacetamide (BSTFA) derivation, and their toxic effects lead to the lower cell survival ratios after exposing to phenol (64.2% ∼ 68.9%) than to aniline and mixture (72.7% ∼ 78.0%). The stable performance is associated with the more secretion of extracellular polymeric substances (EPS) and the adsorption of pollutants on EPS, and this was indicated from the higher fluorescence intensity in three-dimensional excitation-emission matrix (3D-EEM). Moreover, the Halomonas and Azoarcus show high abundance and play important roles in the removal of both NO3− and aromatic compounds. Besides, quantitative real time PCR (RT-qPCR) results demonstrate the key role of highly abundant nosZ and nirS genes in denitrification. The toxic organics in industrial wastewaters are potentially feasible carbon sources for denitrification even under high-salinity stress.

Engineering an alginate/β-glycerophosphate/dextran injectable hydrogel-delivery for cardiac therapies after acute myocardial infarctions

Human mesenchymal stem cell therapy (hMSCs) enables the transmission of alginate (A)/dextran (D)/β- glycerophosphate (β-GP) to the human myocardials infarcts. The fabricated hMSCs-AD@β-GP exhibited pixelation rate, pore size, absorbency, and aggregation rate values of 65.3%, 146.2%, 92.0%, and 29.1% with 1%, respectively. The hMSCs-AD@β-GP produced were physiochemically examined and were found to be highly stable, verifying the usefulness of the nanomaterials for cardiac regenerations. The in vitro studies of hMSCs- AD@β-GP hydrogels have indicated that the cell survival ratio improved, and the positive findings of ejection fraction, fibrosis, and vessel density with lowered infraction size indicated that the heart regenerative activity also improved significantly after myocardial infraction. The synergic effect of the hydrogel with hMSCs-AD@β- GP may, therefore, be suitable to treat patients with severe myocardial infarctions.

Knockdown of Circular RNA Hsa_circ_0000714 Can Regulate RAB17 by Sponging miR-370-3p to Reduce Paclitaxel Resistance of Ovarian Cancer Through CDK6/RB Pathway.

PurposePaclitaxel resistance in ovarian cancer has become an urgent clinical problem. This study investigated the regulatory effects of RAB17 on the non-coding RNA network of the paclitaxel-resistant ovarian cancer cell A2780/PTX.MethodsMicroarray analysis was used to identify differentially expressed genes in paclitaxel-resistant cell A2780/PTX compared to the parent paclitaxel-sensitive cell A2780. Quantitative real-time PCR and Western blot were used to measure the expression of related mRNAs and proteins. The CCK8 assay was used to determine cell survival ratios and drug resistance indices in ovarian cancer cells. The clone forming assay was used to analyze the cell clone proliferation. Flow cytometry was used to analyze the cell cycle. Dual-luciferase reporter gene assays evaluated the relationship between the genes.ResultsRAB17 is highly expressed in A2780/PTX cells. RAB17 knockdown increased the cell sensitivity to paclitaxel, inhibited proliferation, and caused cell cycle arrest in the G1 phase in A2780/PTX. Western blot confirmed that RAB17 influenced cell behavior by activating the CDK6/RB signaling pathway. Bioinformatics analyses identified RAB17 as a new target by the microRNA miR-370-3p, and the latter was predicted to interact with circular RNA hsa_circ_0000714. Hsa_circ_0000714 indeed acted as a miRNA sponge for miR-370-3p allowing its regulation of RAB17 expression. This regulation was accomplished through the CDK6/RB signaling pathway.ConclusionHsa_circ_0000714 acts as a sponge for miR-370-3p, and regulates RAB17 expression through the CDK6/RB signaling pathway, which plays a role in the malignant progression of the paclitaxel-resistant ovarian cancer cell A2780/PTX.

Deltex E3 Ubiquitin Ligase 3L confers radioresistance in prostate cancer via Akt pathway

Purpose: To determine the effect of Deltex E3 Ubiquitin Ligase 3L (DTX3L) on the radioresistance of prostate cancer (PCa).Methods: A PCa cell model of radioresistance was established via exposure of cancer cell lines to fractionated radiation. The MTT {(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)} assay and western blotting were performed to evaluate the impact of DTX3L on cell survival and DNA damage repair. The molecular mechanism of action was evaluated by western blotting.Results: DTX3L was elevated in PCa cell lines compared with normal primary prostate epithelial cells (p &lt; 0.01). The survival of PCa cells exposed to radiation was promoted by overexpression of DTX3L, while knockdown of DTX3L abrogated the radioresistance. Moreover, overexpression of DTX3Ldecreased phosphorylation of histone H2AX (γH2AX) and increased Rad51 levels (p &lt; 0.01). However, knockdown of DTX3L reversed the accumulation of γH2AX and Rad51. Phosphorylation of AKT was promoted by DTX3L overexpression, but was reduced by DTX3L knockdown (p &lt; 0.01). Inhibition of AKT (protein kinase B) counteracted the promotion ability of DTX3L on the radioresistance of PCa cells via decreased cell survival ratio, and also inhibited DNA damage repair via accumulation of γ-H2AX and depletion of Rad51 (p &lt; 0.01).Conclusion: DTX3L increases the resistance of prostate cancer to radiotherapy and DNA damage repair in PCa via AKT pathway, indicating a potential therapeutic strategy to overcome radioresistance in PCa.&#x0D; Keywords: DTX3L (Deltex E3 Ubiquitin Ligase 3L), DNA damage, Phosphorylation, Radioresistance, AKT, Protein kinase B, Prostate cancer

Identification of a nuclear localization signal in the Plasmodium falciparum CTP: phosphocholine cytidylyltransferase enzyme

The phospholipid biosynthesis of the malaria parasite, Plasmodium falciparum is a key process for its survival and its inhibition is a validated antimalarial therapeutic approach. The second and rate-limiting step of the de novo phosphatidylcholine biosynthesis is catalysed by CTP: phosphocholine cytidylyltransferase (PfCCT), which has a key regulatory function within the pathway. Here, we investigate the functional impact of the key structural differences and their respective role in the structurally unique pseudo-heterodimer PfCCT protein in a heterologous cellular context using the thermosensitive CCT-mutant CHO-MT58 cell line. We found that a Plasmodium-specific lysine-rich insertion within the catalytic domain of PfCCT acts as a nuclear localization signal and its deletion decreases the nuclear propensity of the protein in the model cell line. We further showed that the putative membrane-binding domain also affected the nuclear localization of the protein. Moreover, activation of phosphatidylcholine biosynthesis by phospholipase C treatment induces the partial nuclear-to-cytoplasmic translocation of PfCCT. We additionally investigated the cellular function of several PfCCT truncated constructs in a CHO-MT58 based rescue assay. In absence of the endogenous CCT activity we observed that truncated constructs lacking the lysine-rich insertion, or the membrane-binding domain provided similar cell survival ratio as the full length PfCCT protein.

Chemical constituents from ethyl acetate extraction of Prunus mume

Eight compounds were isolated from the ethyl acetate extraction of Prunus mume by column chromatography. On the basis of physicochemical properties and spectrum analysis, these compounds were identified as isoquercitrin-6″-O-benzoate(1), pinoresinol(2), naringin(3), ethyl-β-D-glucopyranoside(4), astragalin(5), quercetin(6), hypericin(7), and rutin(8). Among them, compound 1 was a new natural product, and compounds 2-5 were isolated from this plant for the first time. In vitro study, compounds 1, 3, 5-8 could significantly increase the cell survival ratio.

Melatonin attenuates inflammation-related venous endothelial cells apoptosis through modulating the MST1-MIEF1 pathway.

Chronic venous disease (CVD) is a prevalent and potentially debilitating condition that affects millions of individuals. An excessive endothelial inflammatory response is reportedly involved in the development of CVD. In this study, we explored the effect and mechanism of melatonin on venous endothelial damage induced by tumor necrosis factor α (TNF-α). Our data demonstrated that inflammation injury triggered mitochondrial dysfunction, activated reactive oxygen species-related oxidative damage, inhibited mitochondrial potential and ultimately initiated caspase-involved cellular death. Interestingly, melatonin preserved inflammation-attacked mitochondrial performance and thus increased cell survival under TNF-α. Cellular experiments illustrated that inflammation injury promoted the levels of mammalian sterile 20-like kinase 1 (MST1) and mitochondrial elongation factor 1 (MIEF1); active MST1-MIEF1 pathway disturbed mitochondria-related energy production, leading to mitochondria-induced cell damage. Interestingly, melatonin effectively suppressed MST1-MIEF1 axis and thus improved cell survival ratio under TNF-α-mediated inflammation injury. Reactivation of MST1-MIEF1 pathway attenuated melatonin-related endothelial protective actions. Herein, our results illuminate that melatonin is an effective approach to attenuate inflammation-related venous endothelial cell damage through handling the MST1-MIEF1 signaling pathway.

Heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to pharmorubicin by promoting autophagy via PI3K/Akt pathway.

BackgroundConcerns about breast cancer had become the most dangerous cancer to women over the world, more and more anti‐cancer agents are developed to treat this malignancy. Pharmorubicin is a cytotoxic drug, widely used in the treatment of breast cancer, but its role is limited because of chemoresistance produced by cells. This study focused on exploring the influence of autophagy on the resistance of pharmorubicin in breast cancer cells.MethodsThe cell survival of breast cancer cells was detected by MTT. The mRNA expression of heme oxygenase‐1 (HO‐1) was tested by qRT‐PCR. The protein expression of HO‐1, autophagic proteins (LC3‐I,LC3‐II and Beclin‐1), PI3K and Akt was detected by Western blot. Cell autophagy was examined by Cyto‐ID Autophagy Detection Kit.ResultsAfter being treated with pharmorubicin, the expression of HO‐1 and autophagy related proteins was significantly enhanced, but the cell survival ratio in the two cell lines decreased. After autophagy was inhibited, HO‐1 expression in two cells was down‐regulated. When pharmorubicin‐resistant cells were transfected with si‐HO‐1, the cell survival decreased and the protein expression of HO‐1, autophagic proteins (LC3‐II/LC3‐I and Beclin‐1) as well as autophagy were all down‐regulated, while in pharmorubicin‐resistant cells transfected with pcDNA3.1‐HO‐1, the results were reverse. When the PI3K or Akt was inhibited, PI3K, p‐Akt, HO‐1, autophagic proteins and autophagy were decreased remarkably.ConclusionIt was proved that HO‐1 induction mediated chemoresistance of pharmorubicin in breast cancer cells by promoting autophagy via PI3K/Akt pathway.

Long-Term Priming by Three Small Molecules Is a Promising Strategy for Enhancing Late Endothelial Progenitor Cell Bioactivities.

Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, and oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of CD34+ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against H2O2-induced oxidative stress via the augmented expression of Bcl-2, a prosurvival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.

An in vitro focus on doxorubicin hydrochloride delivery of novel pH‐responsive poly(2‐succinyloxyethylmethacrylate) and poly[(N‐4‐vinylbenzyl),N,N‐diethylamine] diblock copolymers

AbstractNovel pH‐responsive poly(2‐succinyloxyethylmethacrylate)‐b‐poly[(N‐4‐vinylbenzyl),N,N‐diethylamine] [poly(SEMA‐b‐VEA)] diblock copolymers were synthesized via reversible addition fragmentation transfer (RAFT) polymerization to investigate their self‐assembly micellar behavior. The self‐assembly behaviors of synthesized diblock copolymers with distinct molecular weights (labeled (1) to) were confirmed by 1H NMR spectroscopy, TEM and dynamic light scattering measurements. Doxorubicin hydrochloride (DOX) loading capacity was evaluated, and the in vitro cytotoxicity effect of DOX‐loaded diblock copolymer was also studied by assessing the survival rate of the breast cancer cell line MCF‐7 with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The results exhibited remarkable controlled release in the MTT assay. The DOX encapsulation efficiency was calculated to be 96.4%. The size and zeta potential of DOX‐loaded poly(SEMA‐b‐VEA) diblock copolymers were 204 nm and +5.7 mV at a pH of 7.4. DOX release values after 440 h at pH 7.4, 5.4 and 4 were 22.15%, 31.43% and 47.06%, respectively. The released values of DOX‐loaded poly(SEMA‐b‐VEA) and at pH 7.4 were 22.15%, 20.5% and 17.5%, respectively. Cell survival ratios were 18.9%, 23.16% and 16.92% after 72 h. Poly(SEMA‐b‐VEA) copolymers can be considered in nanomedicine applications due to their excellent pH‐responsive micellar behavior. © 2017 Society of Chemical Industry

Precise Regulation of miR-210 is Critical for the Cellular Homeostasis Maintenance and Transplantation Efficacy Enhancement of Mesenchymal Stem Cells in Acute Liver Failure Therapy

Stem cell transplantation is a promising clinical strategy to cure acute liver failure. However, a low cell survival ratio after transplantation significantly impairs its therapeutic efficacy. This is partly due to insufficient resistance of transplanted stem cells to severe oxidative and inflammatory stress at the injury sites. In the current study, we demonstrated that a small molecule zeaxanthin dipalmitate (ZD) could enhance the defensive abilities against adverse stresses of human adipose-derived mesenchymal stem cells (hADMSCs) in vitro and increase their therapeutic outcomes of acute liver failure after transplantation in vivo. Treatment with ZD dramatically improved cell survival and suppressed apoptosis, inflammation, and reactive oxygen species (ROS) production of hADMSCs through the PKC/Raf-1/MAPK/NF-κB pathway to maintain a reasonably high expression level of microRNA-210 (miR-210). The regulation loop between miR-210 and cellular/mitochondrial ROS production was found to be linked by the ROS inhibitor iron–sulfur cluster assembly proteins (ISCU). Pretreatment with ZD and stable knockdown of miR-210 significantly improved and impaired the stem cell transplantation efficacy through the alteration of hepatic cell expansion and injury amelioration, respectively. Vehicle treatment with ZD did not pose any adverse effect on cell homeostasis or healthy animal. In conclusion, elevating endogenous antioxidant level of hADMSCs with ZD significantly enhances their hepatic tissue-repairing capabilities. Maintenance of a physiological level of miR-210 is critical for hADMSC homeostasis.

Stability of biocontrol products carrying Candida sake CPA-1 in starch derivatives as a function of water activity

ABSTRACTThe preservation and shelf-life of formulations of the biocontrol agent Candida sake CPA-1 and starch derivatives as a function of water activity (aW) were studied in terms of the physical stability of the products and cell viability. Formulations of biocontrol products (BCPs), based on combinations of potato starch and pre-gelatinised potato starch (F1 and F2) or maltodextrines (MD) (F3) containing cell protectants, were obtained by fluidised-bed drying. The carriers and the formulated products were stored at 20°C under different aW conditions. The water sorption and water plasticization behaviour of the different products were analysed through the water sorption isotherms and glass transition temperatures (Tg). Likewise, the viability of C. sake over time was determined as a function of the aW. The solubility of the products was also assessed. Although formulations stored at 20°C and low aW (≤ 0.33) exhibited a better shelf-life, a significant decrease in cell survival ratio after 180 storage days was observed. Cold storage (5°C) was required to better maintain the cell viability, thus prolonging the shelf-life of BCPs. Formulations containing MD were the most effective at preserving cell viability and also exhibited the highest water solubility. All the formulations were physically stable at ambient temperature; therefore, the cell stability is the critical point at which to establish both the aW levels and temperature during storage. Packaging the product using high water vapour barrier material and under cold storage would be necessary to ensure a high number of viable cells and an effective and competitive BCP.