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Veno-veous extracorporeal membrane oxygenation (VV-ECMO) has been widely used in the treatment for severe acute respiratory distress syndrome (ARDS). Up to now, the routine access to establish VV-ECMO involves two-sites single lumen cannula via femoral vein and internal jugular venous in adult and children, while few studies about the dual lumen cannula (DLC) in VV-ECMO implemented in adult and children have been reported. On December 16, 2021, an unconscious child with severe ARDS due to multiple trauma caused by fatal falling from a height was admitted to Taihe Hospital. The initial diagnosis was hemorrhagic shock, bilateral hemopneumothorax, sternal fracture, cavity organ perforation, splenic rupture, and pelvic fracture and severe ARDS. Despite mechanical ventilation, he progressed to refractory hypoxemia and was treated with VV-ECMO after successful DLC placement in the right internal jugular vein by the mobile ECMO team of intensive care unit of the Union Hospital eventually. In addition, he received endoscopic sputum aspiration, prone position ventilation, anti-infection and nutritional treatment. His oxygenation gradually improved and he was successfully weaned from ECMO after 11 days. In this case, DLC simplified the process without any related complications, suggesting that it can be safely and effectively used in the treatment of Child's severe ARDS.

Nanoparticles (NPs) have attracted tremendous interest in drug delivery in the past decades. Microfluidics offers a promising strategy for making NPs for drug delivery due to its capability in precisely controlling NP properties. The recent success of mRNA vaccines using microfluidics represents a big milestone for microfluidic NPs for pharmaceutical applications, and its rapid scaling up demonstrates the feasibility of using microfluidics for industrial-scale manufacturing. This article provides a critical review of recent progress in microfluidic NPs for drug delivery. First, the synthesis of organic NPs using microfluidics focusing on typical microfluidic methods and their applications in making popular and clinically relevant NPs, such as liposomes, lipid NPs, and polymer NPs, as well as their synthesis mechanisms are summarized. Then, the microfluidic synthesis of several representative inorganic NPs (e.g., silica, metal, metal oxide, and quantum dots), and hybrid NPs is discussed. Lastly, the applications of microfluidic NPs for various drug delivery applications are presented., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Here, we describe a stress-tolerant, recyclable, and renewable biocatalyst platform based on T7 RNA polymerase-enabled high-density protein display on bacterial spores (TIED). TIED uses high-level T7 RNA polymerase-driven expression of recombinant proteins specifically in sporulating cells to allow spontaneous assembly of recombinant fusion proteins on the Bacillus subtilis spore surface. TIED enables high loading density in the range of 10 6 to 10 7 recombinant enzymes per spore, robust catalytic activity of displayed enzymes comparable to the respective free enzymes, and enhanced kinetic stability of displayed enzymes in methanol and elevated temperatures. Furthermore, we demonstrate TIED enzymes to be not only recyclable but also fully renewable after the loss of activity through induction of germination and sporulation, enabling perpetual regeneration of these immobilized biocatalysts.

Micrometer-resolution 3D printing of functional oxides is of growing importance for the fabrication of micro-electromechanical systems (MEMSs) with customized 3D geometries. Compared to conventional microfabrication methods, additive manufacturing presents new opportunities for the low-cost, energy-saving, high-precision, and rapid manufacturing of electronics with complex 3D architectures. Despite these promises, methods for printable oxide inks are often hampered by challenges in achieving the printing resolution required by today's MEMS electronics and integration capabilities with various other electronic components. Here, a novel, facile ink design strategy is presented to overcome these challenges. Specifically, we first prepare a high-solid loading (∼78 wt%) colloidal suspension that contains polyethyleneimine (PEI)-coated stannic dioxide (SnO 2 ) nanoparticles, followed by PEI desorption that is induced by nitric acid (HNO 3 ) titration to optimize the rheological properties of the printable inks. Our achieved ∼3-5 μm printing resolution is at least an order of magnitude higher than those of other printed oxide studies employing nanoparticle ink-based printing methods demonstrated previously. Finally, various SnO 2 structures were directly printed on a MEMS-based microelectrode for acetylene detection application. The gas sensitivity measurements reveal that the device performance is strongly dependent on the printed SnO 2 structures. Specifically, the 3D structured SnO 2 gas sensor exhibits the highest response of ∼ 29.9 to 100 ppm acetylene with the fastest total response time of ∼ 65.8 s. This work presents a general ink formulation and printing strategy for functional oxides, which further provides a pathway for the additive manufacturing of oxide-based MEMSs.

A protein corona forms around nanoparticles when they are intravenously injected into the bloodstream. The composition of the protein corona dictates the interactions between nanoparticles and the biological systems thus their immune evasion, blood circulation, and biodistribution. Here, we report for the first time the impact of nanoparticle stiffness on protein corona formation using a unique emulsion core silica shell nanocapsules library with a wide range of mechanical properties over four magnitudes (700 kPa to 10 GPa). The nanocapsules with different stiffness showed distinct proteomic fingerprints. The protein corona of the stiffest nanocapsules contained the highest amount of complement protein (Complement C3) and immunoglobulin proteins, which contributed to their high macrophage uptake, confirming the important role of nanocapsules stiffness in controlling the protein corona formation thus their in vitro and in vivo behaviors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Iron oxide nanoparticles have been extensively studied for a wide variety of applications. However, there remains a challenge in developing hierarchical magnetic iron oxide nanoparticles as existing synthetic techniques require harsh, toxic chemical conditions and high temperatures or give poorly defined product with weak magnetic properties. In addition, drug loading is limited to post-loading methods such as chemical conjugation or surface adsorption that have poor loading efficiency and are prone to premature drug release. We report a facile biomimetic method for making iron oxide nanoparticle-loaded silica nanocapsules based on a bimodal catalytic peptide surfactant stabilized nanoemulsion template. Iron oxide nanoparticles can be preloaded into the oil phase of the nanoemulsion at tunable concentrations, and the excellent surface activity of the designed bimodal peptide in combination with sufficient electrostatic repulsion promotes the stability of the nanoemulsions. Biosilicification induced by the catalytic peptide module leads to the formation of silica shell nanocapsules containing a magnetic oil core. The bioinspired silica nanocapsules encapsulating iron oxide nanoparticles demonstrate the next-generation of magnetic nanostructures for drug delivery applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Biomimetic nanomaterials have attracted tremendous research interest in the past decade. We recently developed biomimetic core-shell nanoparticles - silica nanocapsules, using a designer dual-functional peptide SurSi under room temperature, neutral pH and without use of any toxic reagents or chemicals. The SurSi peptide is designed capable of not only stabilizing nanoemulsions because of its excellent surface activity, but also inducing the formation of silica through biosilicification at an oil-water interface. However, it remains challenging to precisely control the peptide-induced nucleation and biosilicification specifically at the oil-water interface, thus forming oil-core silica-shell nanocapsules with uniform size and monodispersity. In this study, the fundamental mechanism of silica formation through a peptide catalyzed biosilicification was systematically investigated, so that the formation of oil-core silica-shell nanocapsules can be precisely controlled. The SurSi peptide induced hydrolysis and nucleation of biomineralized silica particles were monitored to study the biosilicification kinetics. Effects of pH, SurSi peptide concentration and pre-hydrolysis of silica precursors were also studied to optimize the formation of biomimetic silica nanocapsules. The fundamental understanding achieved through these systematic studies provides valuable insights for making core-shell nanoparticles via controlling nucleation and reaction at interfaces., Competing Interests: Declaration of Competing Interest C.-X.Z is an inventor on a patent related to this work filed by The University of Queensland (European Patent Office: EP3046870A1; Australia: AU2014321161B2; United States: US20160193581A1; and Canada: CA2959201A1). Other authors declare no other competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The ability of cells to sense external mechanical cues is essential for their adaptation to the surrounding microenvironment. However, how nanoparticle mechanical properties affect cell-nanoparticle interactions remains largely unknown. Here, we synthesized a library of silica nanocapsules (SNCs) with a wide range of elasticity (Young's modulus ranging from 560 kPa to 1.18 GPa), demonstrating the impact of SNC elasticity on SNC interactions with cells. Transmission electron microscopy revealed that the stiff SNCs remained spherical during cellular uptake. The soft SNCs, however, were deformed by forces originating from the specific ligand-receptor interaction and membrane wrapping, which reduced their cellular binding and endocytosis rate. This work demonstrates the crucial role of the elasticity of nanoparticles in modulating their macrophage uptake and receptor-mediated cancer cell uptake, which may shed light on the design of drug delivery vectors with higher efficiency., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Various pesticide nanocarriers have been developed. However, their pest-control applications remain limited in laboratories. Herein, we developed silica nanocapsules encapsulating fipronil (SNC) and their engineered form, poly(ethyleneimine)-coated SNC (SNC-PEI), based on recombinant catalytic modular protein D4S2 and used them against termite colonies Coptotermes lacteus in fields. To achieve this, an integrated biomolecular bioprocess was developed to produce D4S2 for manufacturing SNC containing fipronil with high encapsulation efficiency of approximately 97% at benign reaction conditions and at scales sufficient for the field applications. PEI coating was achieved via electrostatic interactions to yield SNC-PEI with a slower release of fipronil than SNC without coating. As a proof-of-concept, bait toxicants containing varied fipronil concentrations were formulated and exposed to nine termite mounds, aiming to prolong fipronil release hence allowing sufficient time for termites to relocate the baits into and distribute throughout the colony, and to eliminate that colony. Some baits were relocated into the mounds, but colonies were not eliminated due to several reasons. We caution others interested in producing bait toxicants to be aware of the multilevel resistance mechanisms of the Coptotermes spp. "superorganism".

The physicochemical properties of nanoparticles play critical roles in regulating nano-bio interactions. Whereas the effects of the size, shape, and surface charge of nanoparticles on their biological performances have been extensively investigated, the roles of nanoparticle mechanical properties in drug delivery, which have only been recognized recently, remain the least explored. This review article provides an overview of the impacts of nanoparticle mechanical properties on cancer drug delivery, including (1) basic terminologies of the mechanical properties of nanoparticles and techniques for characterizing these properties; (2) current methods for fabricating nanoparticles with tunable mechanical properties; (3) in vitro and in vivo studies that highlight key biological performances of stiff and soft nanoparticles, including blood circulation, tumor or tissue targeting, tumor penetration, and cancer cell internalization, with a special emphasis on the underlying mechanisms that control those complicated nano-bio interactions at the cellular, tissue, and organ levels. The interesting research and findings discussed in this review article will offer the research community a better understanding of how this research field evolved during the past years and provide some general guidance on how to design and explore the effects of nanoparticle mechanical properties on nano-bio interactions. These fundamental understandings, will in turn, improve our ability to design better nanoparticles for enhanced drug delivery.

Three-dimensional (3D) tumor spheroids offer unprecedented capability for drug screening because of their unique features such as spatial 3D structure, relevant physiological responses, more complex intercellular network, and stroma-cancer cell interactions. Microfluidic technology provides a facile strategy to make uniform tumor spheroids with potential of high-throughput production. In this article, we develop a microfluidic approach to produce core-shell alginate particles, which allows the separate confinement of different cells in the core and shell structure. To reconstitute the complex tumor structure, we encapsulated tumor cells in the core and stromal fibroblast cells in the shell. These coculture tumor spheroids were applied for drug evaluation showing similar drug resistance as those prepared using conventional methods in well plates. These results demonstrated that our microfluidic approach are facile and versatile for making various tumor spheroids with uniform size but different components to better mimic tumor microenvironment. Moreover, the production rate of around 200 spheroids/min indicates the great potential of this approach for high-throughput drug screening.

Nanoparticle tumor accumulation relies on a key mechanism, the enhanced permeability and retention (EPR) effect, but it remains challenging to decipher the exact impact of the EPR effect. Animal models in combination with imaging modalities are useful, but it is impossible to delineate the roles of multiple biological barriers involved in nanoparticle tumor accumulation. Here we report a microfluidic tumor-vasculature-on-a-chip (TVOC) mimicking two key biological barriers, namely, tumor leaky vasculature and 3D tumor tissue with dense extracellular matrix (ECM), to study nanoparticle extravasation through leaky vasculature and the following accumulation in tumor tissues. Intact 3D tumor vasculature was developed with selective permeability of small molecules (20 kDa) but not large ones (70 kDa). The permeability was further tuned by cytokine stimulation, demonstrating the independent control of the leaky tumor vasculature. Combined with tumor spheroids in dense ECM, our TVOC model is capable of predicting nanoparticles' in vivo tumor accumulation, thus providing a powerful platform for nanoparticle evaluation.

Objectives: Olfactory dysfunction (ODF) has been reported in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). However, the comparison of olfactory function and olfactory-related gray matter (GM) between patients with NMO and MS needed to be further elucidated., Materials and Methods: Thirty-seven patients with NMO and 37 with MS were enrolled. Olfactory function was evaluated with a Japanese T&T olfactometer test kit, and the neuroanatomical features of olfactory-related GM were assessed using voxel-based morphometry., Results: Olfactory deficits were found in 51.4% of patients with NMO and 40.5% of patients with MS. Patients with NMO with ODF had significantly smaller olfactory bulbs than patients with MS with ODF (p = 0.031). Olfactory-related GM atrophy was found in patients with NMO in several regions of the right orbitofrontal cortex and right superior frontal gyrus; in patients with MS, reduced GM volume was found in the right parahippocampal gyrus and piriform cortex (p < 0.05, cluster size > 200 voxels)., Conclusions: Olfactory deficits are common in both NMO and MS. However, the neuroanatomical features related to olfactory deficits differ greatly between the two diseases.

Excessive forces may cause root resorption and insufficient forces would introduce no effect in orthodontics. The objective of this study was to investigate the optimal orthodontic forces on a maxillary canine, using hydrostatic stress and logarithmic strain of the periodontal ligament (PDL) as indicators. Finite element models of a maxillary canine and surrounding tissues were developed. Distal translation/tipping forces, labial translation/tipping forces, and extrusion forces ranging from 0 to 300 g (100 g=0.98 N) were applied to the canine, as well as the force moment around the canine long axis ranging from 0 to 300 g·mm. The stress/strain of the PDL was quantified by nonlinear finite element analysis, and an absolute stress range between 0.47 kPa (capillary pressure) and 12.8 kPa (80% of human systolic blood pressure) was considered to be optimal, whereas an absolute strain exceeding 0.24% (80% of peak strain during canine maximal moving velocity) was considered optimal strain. The stress/strain distributions within the PDL were acquired for various canine movements, and the optimal orthodontic forces were calculated. As a result the optimal tipping forces (40-44 g for distal-direction and 28-32 g for labial-direction) were smaller than the translation forces (130-137 g for distal-direction and 110-124 g for labial-direction). In addition, the optimal forces for labial-direction motion (110-124 g for translation and 28-32 g for tipping) were smaller than those for distal-direction motion (130-137 g for translation and 40-44 g for tipping). Compared with previous results, the force interval was smaller than before and was therefore more conducive to the guidance of clinical treatment. The finite element analysis results provide new insights into orthodontic biomechanics and could help to optimize orthodontic treatment plans.

The physicochemical properties of nanoparticles (size, charge, and surface chemistry, etc.) influence their biological functions often in complex and poorly understood ways. This complexity is compounded when the nanostructures involved have variable mechanical properties. Here, we report the synthesis of liquid-filled silica nanocapsules (SNCs, ∼ 150 nm) having a wide range of stiffness (with Young's moduli ranging from 704 kPa to 9.7 GPa). We demonstrate a complex trade-off between nanoparticle stiffness and the efficiencies of both immune evasion and passive/active tumor targeting. Soft SNCs showed 3 times less uptake by macrophages than stiff SNCs, while the uptake of PEGylated SNCs by cancer cells was independent of stiffness. In addition, the functionalization of stiff SNCs with folic acid significantly enhanced their receptor-mediated cellular uptake, whereas little improvement for the soft SNCs was conferred. Further in vivo experiments confirmed these findings and demonstrated the critical role of nanoparticle mechanical properties in regulating their interactions with biological systems.

Double emulsions with a hierarchical core-shell structure have great potential in various applications, but their broad use is limited by their instability. To improve stability, water-in-oil-in-water (W/O/W) emulsions with an ultrathin oil layer of several hundred nanometres were produced by using a microcapillary device. The effects of various parameters on the generation of ultrathin-shell double emulsions and their droplet size were investigated, including the proper combinations of inner, middle and outer phases, flow rates and surfactants. The surfactant in the middle oil phase was found to be critical for the formation of the ultrathin-shell double emulsions. Furthermore, the stability of these double emulsions can be notably improved by increasing the concentration of the surfactant, and they can be stable for months. This opens up new opportunities for their future applications in cosmetics, foods and pharmaceuticals., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Backgrounds: Guillain-Barré syndrome (GBS) is a postinfectious immune-mediated peripheral neuropathy. Interleukin (IL)-27 and IL-35 have been recognized as novel members of IL-12 family. We evaluated the serum and cerebral spinal fluid (CFS) concentrations of IL-27 and IL-35 in GBS and analyze their correlations with clinical characteristics., Methods: Serum samples from 50 patients with GBS including 9 acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 33 acute motor axonal neuropathy (AMAN) and 8 unclassified and 35 age- and sex-matched healthy controls were collected. Thirty CSF samples from these patients and 25 patients with other noninflammatory neurological disorders (ONNDs) as disease controls were collected after lumbar puncture. Serum and CSF IL-27 and IL-35 concentrations were measured using human IL-27 or IL-35 ELISA., Results: Serum IL-27 concentrations were elevated (p=0.002) whereas serum IL-35 concentrations were decreased (p=0.031) in patients with GBS comparing with healthy controls, particularly in patients exhibiting AMAN (p=0.012). Additionally, serum IL-35 concentrations were negatively correlated with disease severity and outcomes in patients with AMAN (r=-0.358, p=0.041; r=-0.416, p=0.016)., Conclusions: IL-27 might be pathogenic, whereas IL-35 be protective in GBS. Additionally, serum IL-35 concentrations may be important biomarkers for the severity and outcomes of AMAN., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Silica nanocapsules have attracted significant interest due to their core-shell hierarchical structure. The core domain allows the encapsulation of various functional components such as drugs, fluorescent and magnetic nanoparticles for applications in drug delivery, imaging and sensing, and the silica shell with its unique properties including biocompatibility, chemical and physical stability, and surface-chemistry tailorability provides a protection layer for the encapsulated cargo. Therefore, significant effort has been directed to synthesize silica nanocapsules with engineered properties, including size, composition and surface functionality, for various applications. This review provides a comprehensive overview of emerging methods for the manufacture of silica nanocapsules, with a special emphasis on different interfacial engineering strategies. The review starts with an introduction of various manufacturing approaches of silica nanocapsules highlighting surface engineering of the core template nanomaterials (solid nanoparticles, liquid droplets, and gas bubbles) using chemicals or biomolecules which are able to direct nucleation and growth of silica at the boundary of two-phase interfaces (solid-liquid, liquid-liquid, and gas-liquid). Next, surface functionalization of silica nanocapsules is presented. Furthermore, strategies and challenges of encapsulating active molecules (pre-loading and post-loading approaches) in these capsular systems are critically discussed. Finally, applications of silica nanocapsules in controlled release, imaging, and theranostics are reviewed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Double emulsions are normally considered as metastable systems and this limit in stability restricts their applications. To enhance their stability, the outer shell can be converted into a mechanically strong layer, for example, a polymeric layer, thus allowing improved performance. This conversion can be problematic for food and drug applications, as a toxic solvent is needed to dissolve the polymer in the middle phase and a high temperature is required to remove the solvent. This process can also be highly complex, for example, involving UV initiation of polymeric monomer crosslinking. In this study, we report the formation of biocompatible, water-in-oil-in-water (W/O/W) double emulsions with an ultrathin layer of fish oil. We demonstrate their application for the encapsulation and controlled release of small hydrophilic molecules. Without a trigger, the double emulsions remained stable for months, and the release of small molecules was extremely slow. In contrast, rapid release was achieved by osmolarity shock, leading to complete release within 2 h. This work demonstrates the significant potential of double emulsions, and provides new insights into their stability and practical applications., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To explore a simpler, more economic and reproducible method to reproduce a model of high oxygen induced acute lung injury (HALI) in rats., Methods: An animal feeding box equipped with a controllable high oxygen was designed. 100 Sprague-Dawley (SD) rats were divided into normal control group and HALI group by random number table method, with 50 rats in each group. Each group was randomly subdivided into five subgroups according to the duration of exposure to high oxygen, namely 0, 24, 48, 72 and 96-hour subgroups, with 10 rats in each subgroup. The rats in normal control group were kept in cages with ambient air, and the rats in HALI group were kept in an oxygen tank in which the oxygen concentration was higher than 90% volume ratio, with the temperature maintained at 25-27?centigrade, humidity of 50%-70%, and CO2 concentration < 0.5% for 23.5 hours every day. The arterial blood of rats was collected for analysis of blood gas at all time points, and the oxygenation index (OI) and respiratory index (RI) were calculated. Then the rats were sacrificed and the right lung was harvested, which was sectioned and stained with hematoxylin and eosin (HE). The changes in histopathology were observed with light microscopy, and pathological score was recorded. The left lung was harvested for the measurement of the wet/dry weight ratio (W/D)., Results: With the prolongation of high oxygen exposure time, the degree of lung injury in HALI group was gradually increased, and the degree of derangement of alveolar structure appeared in an increasing degree, with destruction of the alveolar wall, widening of alveolar space, and appearance of edema, and inflammatory cell infiltration. A small quantity of red blood cells exudation could be found in some rats. The pathologic changes were most obvious at 48-72 hours after exposure. With the prolongation of high oxygen exposure time (0, 24, 48, 72, 96 hours), the OI (mmHg, 1 mmHg = 0.133 kPa) in HALI group was gradually decreased (446.67±29.93, 306.19±37.23, 269.70±29.00, 253.81±43.40 and 245.58±35.25), RI, pathological score of lung tissue and W/D ratio were gradually increased [RI: 0.25±0.04, 0.31±0.06, 0.38±0.06, 0.46±0.07 and 0.44±0.03; pathological score of lung tissue: 0.00±0.00, 0.90±0.74, 2.90±1.20, 4.70±1.57 and 4.80±1.23; lung W/D ratio: 3.84±0.61, 4.14±0.46, 4.56±0.34, 5.32±0.27 and 5.18±0.25]. Statistically significant differences were found in 72-hour group as compared with that of other groups (all P < 0.05), while no significant difference was found between 96 hours and 72 hours groups (all P > 0.05). There were significant differences in changes between 24, 48, 72, and 96 hours as compared with those of the normal control group: OI (mmHg): 24 h 306.19±37.23 vs. 435.65±25.34 and 96 h 245.58±35.25 vs. 465.42±24.75; RI: 24 h 0.31±0.06 vs. 0.24±0.04 and 96 h 0.44±0.03 vs. 0.24±0.06. The same as true in pathological scores of lung tissue: 24 h 0.90±0.74 vs. 0.00±0.00 and 96 h 4.80±1.23 vs. 0.00±0.00; lung W/D ratio: 24 h 4.14±0.46 vs. 3.79±0.44 and 96 h 5.18±0.25 vs. 4.12±0.91, all P < 0.05., Conclusions: A self-designed high oxygen box is simple, easy to operate and reproduction of HALI model can be attained. Sustained exposure to high concentrations of oxygen (≥ 90%) for 24 hours can replicate the HALI model successfully, and the most serious injury appears at 48-72 hours after exposure.

The saturated free fatty acid (FFA), palmitate, could induce apoptosis in various cell types, but little is known about its effects on human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). Here, we investigated whether palmitate induced apoptosis and endoplasmic reticulum (ER) stress in hUC-MSCs. hUC-MSCs were stained by labeled antibodies and identified by flow cytometry. After administration with palmitate, apoptotic cell was assessed by flow cytometry using the Annexin V-FITC/7-AAD apoptosis detection kit. Relative spliced XBP1 levels were analyzed using semi-quantitative RT-PCR. The mRNA of BiP, GRP94, ATF4 and CHOP were analyzed by real-time PCR. Relative BiP and CHOP protein were analyzed using Western blot analysis. The results showed that hUC-MSCs were homogeneously positive for MSC markers; palmitate increased apoptosis of hUC-MSCs and activated XBP1 splicing, BiP, GRP94, ATF4 and CHOP transcription. These findings suggest that palmitate induces apoptosis and ER stress in hUC-MSCs.

Purpose: Our purpose was to investigate whether the NO donor, 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), restored cardiac function following global ischemia in an isolated rat heart model and whether intracellular messengers were involved in its effect., Methods: Isolated rat hearts (n = 36) were randomly divided into six groups. The sham control group was perfused with modified Krebs-Henseleit bicarbonate buffer (KHB) alone. The ischemic control group and the NOC7 groups were subjected to 35 min of global ischemia, followed by 30 min of reperfusion with KHB alone, or reperfusion with KHB including NOC7 at 0.2, 2, 20, or 200 microM, respectively. Left ventricular developed pressure (LVDP), the maximum and the minimal rate of rise in LVP (+/-dP/dt), and coronary flow were measured continuously. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were measured in myocardium homogenate, using enzyme immunoassay (EIA) methods., Results: NOC7 at 2 and 20 microM rescued myocardial performance (LVDP, 111.9 +/- 10.5% and 124.3 +/- 12.5% of baseline, respectively; P < 0.05 vs ischemic control) at 30 min after reperfusion. However, NOC7 at 200 microM reduced the LVDP to 55.3 +/- 6.0% of baseline. Coronary flows remain unchanged. The cAMP levels increased significantly from 0.83 +/- 0.44 pmol x mg(-1) protein in the ischemic control group to 1.79 +/- 0.39, 1.86 +/- 0.25, and 2.63 +/- 0.24 pmol x mg(-1) protein, in the groups with NOC7 at 2, 20, and 200 microM, respectively (P < 0.05). The cGMP level increased from 1.49 +/- 0.61 pmol x mg(-1) protein in the ischemic control group to 3.92 +/- 0.66 pmol x mg(-1) protein in the group with NOC7 at 200 microM alone (P < 0.05)., Conclusion: NOC7 appeared to exert a biphasic effect on the contractile force of the isolated rat heart after 35-min global ischemia. The balance between intracellular cAMP and cGMP levels seemed to be involved in its mechanism.