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1.
Brain Res ; : 146677, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32001244

RESUMO

Neurotransmitters such as oxytocin (OT), vasopressin (AVP), and dopamine (DA) within the mesolimbic system have deeply conserved roles in regulating mating related behavior. However, comparative studies among monogamous and polygamous animals focus mainly on Microtus, very little research has been done in gerbils. Here, we measured the body weight, body length, tail length, serum hormone concentrations, and the immunoreactive (ir)-cells of OT, AVP, and tyrosine hydroxylase (TH) in the brain of the polygamous great gerbil (Rhombomys opimus), promiscuous midday gerbil (Meriones meridianus), and monogamous Mongolian gerbil (Meriones unguiculatus). The body weight, body length, tail length, and serum AVP concentrations were greater in the great gerbil than in the midday gerbil and Mongolian gerbil. The numbers of OT and AVP cells in the paraventricular nuclei (PVN) and supraoptic nuclei (SON) of hypothalamus was greater in the Mongolian gerbil than in the great gerbil and midday gerbil. Similarly, the numbers of TH cells in the PVN, medial preoptic area (MPOA), and ventral tegmental area (VTA) was greater in the Mongolian gerbil than in the great gerbil and midday gerbil. To summarize, the numbers of OT and AVP cells in PVN and SON, and the TH cells in PVN, MPOA and VTA in the monogamous Mongolian gerbil are greater than in the polygamous great gerbil and promiscuous midday gerbil.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32006144

RESUMO

PURPOSE: Although current guidelines recommend ticagrelor in addition to aspirin as the antiplatelet strategy for medically managed acute coronary syndrome (MMACS) patients, clinical evidence specific to this special population is lacking. Whether potent oral P2Y12 inhibitors should be used in MMACS patients is still under debate. METHODS: We conducted a comprehensive search in PubMed, Embase, Web of Science, and Cochrane Library to identify studies exploring the efficacy or safety of ticagrelor and prasugrel versus clopidogrel or placebo in MMACS patients. The primary efficacy endpoint was major adverse cardiovascular events (MACE) defined by each study, and the safety endpoint was TIMI non-CABG major bleeding. RESULTS: A total of 6102 records were screened, and 4 studies including 46,346 patients were finally included. The use of potent oral P2Y12 inhibitors significantly lowers the risk of MACE compared with clopidogrel (HR: 0.90; 95% CI: 0.82-0.98; P = .018; I2 = 0%). A significant reduction in risks of all-cause death and myocardial infarction was also observed with the use of potent oral P2Y12 inhibitors compared with clopidogrel. No significant difference in risks of stroke or TIMI non-CABG major bleeding (HR: 1.24; 95% CI: 0.90-1.73; P = .191; I2 = 0%) was observed between potent oral P2Y12 inhibitors and clopidogrel. CONCLUSION: Potent oral P2Y12 inhibitors, especially ticagrelor, decrease the risk of ischemic events in MMACS patients as compared with clopidogrel, without significantly increasing major bleeding.

3.
Physiol Behav ; : 112848, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32088172

RESUMO

Quinestrol and levonorgestrel (EP-1, at a ratio of 1:2) are often used as anti-fertility compounds (sterilants) in rodents. As most of the research has focused on the sterility and damage caused in parental reproductive organs, there is little research on the effect of these contraceptive hormones on maternal behavior and offspring's early development. In this study, we examined maternal behavior after treatment with different doses of EP-1 (10 ml/kg) at postnatal days 3 and 10, separately. Various parameters were measured after treatment, including oxytocin expression, serum levels of estradiol and luteinizing hormone (LH), ovary damage after weaning of offspring, as well as the development and ultrasonic vocalizations (USVs) of midday gerbil (Meriones meridianus) offspring. At postnatal days 5 and 12, the EP-1 increased maternal licking, grooming, and retrieving behavior, while reducing contacting behavior. Oxytocin expression in the hypothalamic paraventricular and supraoptic nuclei increased, while the levels of estradiol and LH decreased. The ovaries and the development of follicles were clearly affected by the treatment. The EP-1 significantly reduced the pups' body weight, the amount and pulse duration of USVs, while the frequency range variation of USVs was increased. Overall, treatment with EP-1 during lactation significantly affected maternal behavior and impaired offspring early development in the midday gerbil.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32054269

RESUMO

Flexible electronics have gained considerable research concern due to their wide prospect for health monitoring, soft robotics and artificial intelligence, wherein flexible pressure sensors are necessary components of wearable devices. It is well known that the synergistic functions and multiscale structures of hybrid materials exert tremendous effects on the performance of flexible devices. Herein, inspired by the unique structure of the faceplate of sunflowers, we construct a hierarchical structure by in-situ grown vertically aligned molybdenum disulfide (MoS2) nanosheets on carbonized silk fabric (MoS2/CSilk), which is applied as the sensing material in flexible pressure sensors. The MoS2/CSilk pressure sen-sor showed high sensitivity and good stability. We demonstrated its applications in monitoring subtle physiology sig-nals, such as pulse wave and voice vibrations. In addition, they were used as electrodes in lithium ion batteries. The MoS2/CSilk electrode delivered ultra-high first-cycle discharge and charge capacities of 2895 and 1594 mA h g-1. The MoS2/CSilk electrode exhibited a high capacity of 810 mA h g-1 with a CE approaching 100% even after 300 cycles, sug-gesting a good high-rate stability. The excellent overall performances are attributed to the unique structure the MoS2/CSilk and the synergistic effect of CSilk and MoS2. The concept and strategy of this work can be extended to the design and fabrication of other multifunctional devices.

5.
Adv Exp Med Biol ; 1240: 83-93, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32060890

RESUMO

Suppression of tumorigenicity 2 (ST2), also known as interleukin-1 receptor-like 1 (IL1RL1), is one of the natural receptors of IL-33. Three major isoforms, ST2L (transmembrane form), sST2 (soluble form), and ST2V, are generated by alternative splicing. Damage to stromal cells induces necrosis and release of IL-33, which binds to heterodimeric ST2L/IL-1RAcP complex on the membrane of a variety of immune cells. This IL-33/ST2L signal induces transcription of the downstream inflammatory and anti-inflammatory genes by activating diverse intracellular kinases and factors to mount an adequate immune response, even in tumor microenvironment. For example, activation of IL-33/ST2L signal may trigger Th2-dependent M2 macrophage polarization to facilitate tumor progression. Notably, sST2 is a soluble form of ST2 that lacks a transmembrane domain but preserves an extracellular domain similar to ST2L, which acts as a "decoy" receptor for IL-33. sST2 has been shown to involve in the inflammatory tumor microenvironment and the progression of colorectal cancer, non-small cell lung cancer, and gastric cancer. Therefore, targeting the IL-33/ST2 axis becomes a promising new immunotherapy for treatment of many cancers. This chapter reviews the recent findings on IL-33/ST2L signaling in tumor microenvironment, the trafficking mode of sST2, and the pharmacological strategies to target IL-33/ST2 axis for cancer treatment.

6.
Neurochem Int ; 135: 104693, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32035889

RESUMO

Maternal anesthetic exposure during pregnancy is associated with an increased risk of cognitive impairment in offspring. The balance of cerebral iron metabolism is essential for the development of brain tissue. Iron deficiency affects the myelinogenesis and nerve tissue development, especially in fetus or infant, which has a key role in cognitive function. We aimed to investigate whether maternal sevoflurane (Sev) exposure caused cognitive impairment in offspring through inducing iron deficiency and inhibiting myelinogenesis. Pregnant mice (gestation stage day 14) were treated with 2% Sev for 6 h. Cognitive function of offspring mice was determined by the Morris water maze and Context fear conditioning test. Iron levels were assayed by Perl's iron staining and synchrotron imaging. Hippocampus and cortex tissues or cerebral microvascular endothelial cells of offspring mice (postnatal day 35) were harvested and subjected to Western blot and/or immunhistochemistry to assess ferritin, transferrin receptor 1(TfR1), Ferroportin-1 (FpN1), myelin basic protein (MBP), tight junction protein ZO-1, occludin, and claudin-5 levels. Beginning with postnatal day 30, the offspring were treated with iron therapy for 30 days, and the indicators above were tested. Our results showed Sev dramatically decreased the iron levels of brain and impaired cognitive function in offspring mice. Sev decreased the expression of heavy chain ferritin (FtH), light chain ferritin (FtL), MBP, ZO-1, occludin, claudin-5, and FpN1, and increased TfR1 in hippocampus and cortex or cerebral microvascular endothelial cells of offspring mice, indicating that Sev caused the iron deficiency and impaired the myelinogenesis in the brain of offspring. Interestingly, iron therapy prompted the myelinogenesis and improved impaired cognitive function at postnatal day 60. Our research uncovered a new mechanism which showed that iron deficiency induced by Sev and myelin formation disorder due to decreased iron of brain may be an important risk factor for cognitive impairment in offspring. It was necessary for offspring to be supplied iron supplement whose mother suffered exposure to sevoflurane during pregnancy.

7.
Cell Mol Life Sci ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062751

RESUMO

Over the last three decades, the scaffold proteins prohibitins-1 and -2 (PHB1/2) have emerged as key signaling proteins regulating a myriad of signaling pathways in health and diseases. Small molecules targeting PHBs display promising effects against cancers, osteoporosis, inflammatory, cardiac and neurodegenerative diseases. This review provides an updated overview of the various classes of PHB ligands, with an emphasis on their mechanism of action and therapeutic potential. We also describe how these ligands have been used to explore PHB signaling in different physiological and pathological settings.

8.
Nanotechnology ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040948

RESUMO

An ultrathin near-perfect MoSe2absorber working in the visible regime is demonstrated theoretically and experimentally, and it consists of a MoSe2/Au bi-layer film. Simulation results show that the absorption of the absorber with 22 nm MoSe2reaches to larger than 99% between 660 nm and 720 nm with a peak value up to 99.9% at 706 nm. Moreover, the facile absorbers are prepared experimentally, whose performances in good agreement with simulations. The polymer-assisted deposition method is used to synthesize MoSe2films, which can reduce the roughness and thus improve the film absorption. Finally, an ultrathin photodetector is fabricated based on this perfect absorber and shows on/off reproducibility and remarkable photocurrent, which is three orders of magnitude higher than the dark current.

9.
PLoS One ; 15(2): e0227262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069297

RESUMO

BACKGROUND: The relationship between serum hemoglobin A1c (HbA1c) and atrial fibrillation (AF) or postoperative AF (POAF) in coronary artery bypass (CABG) patients is still under debate. It is also unclear whether there is a dose-response relationship between circulating HbA1c and the risk of AF or POAF. METHODS AND RESULTS: The Cochrane Library, PubMed, and EMBASE databases were searched. A robust-error meta-regression method was used to summarize the shape of the dose-response relationship. The RR and 95%CI were using a random-effects model. In total, 14 studies were included, totaling 17,914 AF cases among 352,325 participants. The summary RR per 1% increase in HbA1c was 1.16 (95% CI: 1.07-1.27). In the subgroup analysis, the summary RR was 1.13 (95% CI: 1.08-1.19) or 1.12 (95% CI: 1.05-1.20) for patients with diabetes or without known diabetes, respectively. The nonlinear analysis showed a nonlinear (Pnonlinear = 0.04) relationship between HbA1c and AF, with a significantly increased risk of AF if HbA1c was over 6.3%. However, HbA1c (per 1% increase) was not associated with POAF in patients with diabetes (RR: 1.13, P = 0.34) or without known diabetes (RR: 0.91, P = 0.37) among patients undergoing CABG. CONCLUSION: Our results suggest that higher HbA1c was associated with an increased risk of AF, both in diabetes and in without diabetes or with unknown diabetes. However, no association was found between HbA1c and POAF in patients undergoing CABG. Further prospective studies with larger population sizes are needed to explore the association between serum HbA1c level and the risk of POAF.

10.
Sheng Wu Gong Cheng Xue Bao ; 36(1): 143-151, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32072789

RESUMO

In recent years, CRISPR/Cas9-mediated base editing has been developed to a powerful genome editing tool, providing advantages such as without introducing double-stranded DNA break, a donor template and relying on host homologous recombination repair pathway, and has been widely applied in animals, plants, yeast and bacteria. In previous study, our group developed a multiplex automated base editing method (MACBETH) in the important industrial model strain Corynebacterium glutamicum. In this study, to further optimize the method and improve the base editing efficiency in C. glutamicum, we first constructed a green fluorescent protein (GFP) reporter-based detection system. The point mutation in the inactivated GFP protein can be edited to restore the GFP fluorescence. By combining with flow cytometry analysis, the base-editing efficiency can be quickly calculated. Then, the base editor with the target gRNA was constructed, and the editing efficiency with the initial editing condition was (13.11±0.21)%. Based on this result, the editing conditions were optimized and the result indicated that the best medium is CGXII, the best initial OD600 of induction is 0.05, the best induction time is 20 h, and the best IPTG concentration is 0.01 mmol/L. After optimization, the editing efficiency was improved to (30.35±0.75)%, which was 1.3-fold of that in initial condition. Finally, endogenous genomic loci of C. glutamicum were selected to assess if the optimized condition can improve genome editing in other loci. Editing efficiency of different loci in optimized condition were improved to 1.7-2.5 fold of that in original condition, indicating the effectiveness and versatility of the optimized condition. Our research will promote the better application of base editing technology in C. glutamicum.

11.
Cancer Sci ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073706

RESUMO

Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA-373-3p (miR-375-3p) in CRC remains unclear. The current study aimed to explore the potential function of miR-375-3p in 5-fluorouracil (5-FU) resistance. miR-375-3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5-FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration and invasion in vitro. Thymidylate synthase (TYMS) was demonstrated to be a direct target of miR-375-3p, and TYMS knockdown exerted similar effects as miR-375-3p overexpression on the CRC cellular response to 5-FU. Lipid-coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5-FU and miR-375-3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR-375+5-FU/NPs was significantly higher than that of the individual treatments in mouse subcutaneous xenografts derived from HCT116 cells. Our results suggest that restoring miR-375-3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5-FU.

12.
Mar Biotechnol (NY) ; 22(1): 54-66, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31902020

RESUMO

How unisexual animals eliminate deleterious mutations to avoid dead ends is one of the most interesting puzzles in evolutionary genetics. Incorporation of microchromosomes derived from exogenous sperm had been observed in gynogenetic animals, but little is known about their detailed process and hereditary fate. Here, we show a stable genome incorporation case in an artificial clone F of gynogenetic gibel carp (Carassius gibelio). A total of 12 exogenous DNA fragments were screened through a read depth-dependent comparison strategy and confirmed to be specific to the clone F and the paternal blunt snout bream (Megalobrama amblycephala Yin) by SCAR (sequence characterized amplified regions) marker detection. Moreover, these sperm-derived DNA fragments were not detected in some samples in early gynogenetic generations, but they were found to exist in all examined individuals through artificial gynogenetic selections of 13 generations, implying that they might have stably incorporated into the genome of clone F. Furthermore, chromosome localization and sequence characterization indicate that the largest fragment CgA22_34 is derived from blunt snout bream non-LTR retrotransposon and durably incorporated into only one of three homologous chromosomes of gibel carp clone F. Our results suggest that the incorporated sperm-derived DNA fragments by allogynogenesis should increase genetic diversity and introduce new traits into unisexual animals which will benefit genetic breeding of gibel carp. During the process, transposable elements (TEs) may play significant roles in shaping the genome structures. Simultaneously, the incorporated DNA fragments are able to be used as genetic markers to perform selective breeding programs in aquaculture practices of gibel carp.

13.
Biochem Biophys Res Commun ; 523(4): 993-1000, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-31973814

RESUMO

Circular RNAs (circRNAs) are a kind of closed loop endogenous non-coding RNAs have attracted increasing interest in recent years. However, the mechanism of circRNAs in the pathogenesis of multiple cardiovascular diseases, particularly myocardial ischemia, is rarely reported. In the present study, we examined a circular RNA, hsa_circ_0007623, which is highly expressed in hypoxia-induced human umbilical vein endothelial cells (HUVECs) and can act as a sponge for miR-297, which is involved in cardiac repair after acute myocardial ischemia. In hypoxia-stimulated HUVECs, the inhibition of hsa_circ_0007623 expression was found to reduce cell proliferation, migration, and angiogenesis. Further in vivo experiments confirmed the cardioprotective effect of hsa_circ_0007623 expression in isoproterenol-induced acute ischemia mice. Bioinformatics analysis predicted hsa_circ_0007623, sponge miR-297 and miR-297 directly target VEGFA, which was validated by dual-luciferase assay. Subsequently, functional experiments revealed hsa_circ_0007623 silencing could up-regulate miR-297 and down-regulate VEGFA expression, and reduce cell proliferation, migration, and angiogenesis. We concluded that hsa_circ_0007623 can bind to miR-297, promote cardiac repair after acute myocardial ischemia, and protect cardiac function.

14.
Nat Cell Biol ; 22(1): 108-119, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31915373

RESUMO

Owing to the prevalence and high mortality rates of cardiac diseases, a more detailed characterization of the human heart is necessary; however, this has been largely impeded by the cellular diversity of cardiac tissue and limited access to samples. Here, we show transcriptome profiling of 21,422 single cells-including cardiomyocytes (CMs) and non-CMs (NCMs)-from normal, failed and partially recovered (left ventricular assist device treatment) adult human hearts. Comparative analysis of atrial and ventricular cells revealed pronounced inter- and intracompartmental CM heterogeneity as well as compartment-specific utilization of NCM cell types as major cell-communication hubs. Systematic analysis of cellular compositions and cell-cell interaction networks showed that CM contractility and metabolism are the most prominent aspects that are correlated with changes in heart function. We also uncovered active engagement of NCMs in regulating the behaviour of CMs, exemplified by ACKR1+-endothelial cells, injection of which preserved cardiac function after injury. Beyond serving as a rich resource, our study provides insights into cell-type-targeted intervention of heart diseases.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31923463

RESUMO

SOX transcription factors play an irreplaceable role in biological developmental processes. Sox genes have been identified in a wide variety of species; however, their identification and functional analysis in the genome of the Chinese soft-shell turtle (Pelodiscus sinensis) have not been performed. In the present study, the Chinese soft-shell turtle genome was found to contain 17 Sox genes, which were categorized into seven groups according to their phylogenetic relationships. Gene structure and protein motif analysis of the Sox genes showed that within the same phylogenetic group, their exon-intron number and motif structure of the Sox family were relatively conserved, but diverged in the comparison between different groups. Sexual dimorphism expression analysis for the Sox genes displayed that Sox8 and Sox9 were upregulated in the testis, while Sox3, Sox7, Sox11, and Sox13 were upregulated in the ovary. A correlation network analysis of SOX transcription factors with their target genes analysis showed that Sox3 correlated negatively with Sox9 and gata4. Sox11 and Sox7 correlated negatively with gata4. Sox8 and Sox9 correlated positively with gata4. Therefore, the genome-wide identification and functional analysis of the Sox gene family will be useful to further reveal the functions of Sox genes in the Chinese soft-shell turtle.

16.
Oncogene ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911618

RESUMO

Cancer cells with mesenchymal attributes potentially display chemoresistance. Cancer stem cells (CSCs), which are intrinsically resistant to most chemotherapy agents, exhibit considerable phenotypic heterogeneity in their epithelial versus mesenchymal states. However, the drug response of CSCs in the epithelial and mesenchymal states has not been completely investigated. In this study, we found that epithelial-type (E-cadherinhigh/CD133high) CSCs displayed a higher sphere formation ability and chemoresistance than mesenchymal-type (E-cadherinlowCD133high) CSCs. Gene expression profiling of the CSC and non-CSC subpopulations with distinct epithelial-to-mesenchymal transition (EMT) states showed that MyoD family inhibitor domain-containing (MDFIC) was selectively upregulated in epithelial-type CSCs. Knockdown of MDFIC sensitized epithelial-type CSCs to chemotherapy agents. Ectopic expression of MDFIC increased the chemoresistance of mesenchymal-type CSCs. In a tissue microarray, high MDFIC expression was associated with poor prognosis of non-small cell lung cancer (NSCLC) patients. A mechanistic study showed that the MDFIC p32 isoform, which is located in the cytoplasm, interacted with the destruction complex, Axin/GSK-3/ß-catenin. This interaction stabilized ß-catenin by inhibiting ß-catenin phosphorylation at S33/37 and increased the nuclear translocation and transcriptional activity of ß-catenin. Knockdown of ß-catenin decreased MDFIC-enhanced chemoresistance. These results suggested that the upregulation of MDFIC enhanced the chemoresistance of epithelial-type CSCs by elevating ß-catenin activity. Thus, targeting MDFIC-regulated ß-catenin signaling of epithelial-type CSCs may be a potential strategy to overcome chemoresistance in NSCLC.

17.
Mater Sci Eng C Mater Biol Appl ; 108: 110408, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924047

RESUMO

With the increasing requirement of bone repair materials, hydroxyapatite (HA) has been paid widely attention to investigation because of its good bioactivity and osteoconductivity. The structure of HA is a vital factor to expand its application in the field of hard tissue therapy. Thus, many strategies have been utilized in fabricating one-dimensional (1D) and three-dimensional (3D) nanostructured HA. In this paper, we successful synthesize HA with 1D nanofibers and 3D nanostructured microspheres using stearic acid as a template and different phosphates as phosphorus sources under the same synthetic system. The morphology of HA changes from nanofibers with high flexibility to nanostructured microspheres with good sphericity under the synergistic effect of stearic acid and various phosphates. The HA nanofibers and microspheres are promising for applications in biomedical fields. Base on characterization results, the formation mechanisms of HA nanofibers and HA microspheres self-assembled by nanorods are proposed. Furthermore, the HA morphology transition from nanofibers to nanostructured microspheres may be attributed to the formation of polyphosphate-induced water-in-oil microemulsion system in the synthesis process. The finding may provide a new direction to control HA morphology from 1D nanofibers to 3D microspheres based on previous strategies.

18.
Neurochem Int ; 134: 104657, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31904393

RESUMO

Parkinson's disease (PD) is accompanied by iron overload in the brain. However, whether iron accumulation is the cause or effect of PD is still unknown. Iron regulatory protein 2 (IRP2) plays a critical role in keeping iron homeostasis, and our previous data showed that the deletion of the IRP2 gene caused iron deposits in organs of mice. Therefore, we further investigated the role of iron overload induced by IRP2 gene deletion in the development of the MPTP-induced PD mouse model in vivo, and the underlying regulatory mechanisms in primary cultures of astrocytes in vitro. Data from neurobehavioral, immunohistochemistry, TUNEL and Elisa studies showed that MPTP treatment enhanced the symptoms of PD in vivo, increased cell apoptosis and decreased dopamine levels in IRP2-/- mice. In addition, the expression of L-ferritin and iron contents increased significantly in the substantia nigra (SN) of IRP2-/- mice. Moreover, MPTP treatment significantly increased the expression of DMT1 (-IRE) and decreased the expression of TfR1 in IRP2-/- mice. Further investigations with primary cultures of astrocytes from IRP2-/- mice showed that MPP+ increased the expression of L-ferritin and DMT1 (-IRE), and decreased the expression of TfR1. Our results demonstrated that IRP2 gene deletion induced iron accumulation in the SN, which exacerbated the neuronal apoptosis and Parkinsonism symptoms. At the same time, IRP2 gene deletion increased the iron contents in astrocytes around neurons, which further decreased their protection for neurons and increased the cell apoptosis, ultimately forming a vicious cycle that leads to the onset and progression of PD.

19.
ACS Appl Mater Interfaces ; 12(1): 1650-1657, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31822066

RESUMO

Polymer products with precise shape recovery behavior are highly desired for practical applications owing to excellent processability and mechanical properties compared with metallic or inorganic materials. Shape memory polymers (SMPs) provide a solution for this end, but the design and scalable fabrication of photothermal controllable SMPs with accurate, rapid, and repeatable recovery behaviors are still great challenges. In this work, polyurethane/sulfonated carbon nanotube (PU/S-CNT) composite particles are introduced into a cross-linked high-density polyethylene (HDPE) as a functional dispersed phase to realize photo-driven fast shape recovery in cheap polymer composite materials. It is found that microcracks can be induced by the PU/S-CNT composite particles during deformation, generating a particular microparticle in a microcrack (MC-MP) structure. The MC-MP microstructure significantly improves the photothermal conversion efficiency, thereby accelerating the photo-driven shape self-healing of arbitrary nondestructive material damage. It is also found that proper cross-linking of the matrix, HDPE, greatly improves the recovery performance of the materials. This strategy based on the MC-MP microstructure and cross-linked matrix is also instructive for designing new SMPs using other polymer materials.

20.
J Mater Chem B ; 8(2): 270-281, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31802093

RESUMO

Pharmacotherapy towards hypercalcemia treatment mainly caused by osteoporosis and bone tumor is an effective method to regulate in vivo calcium equilibrium. As a clinical therapeutic peptide, salmon calcitonin (sCT) is considered as a quick-acting medicine but it is limited by the short half-life. To address this challenge, we designed an injectable thermo-sensitive hydrogel based on hydroxypropyl chitin (HPCH) and incorporated the complex of sCT and hyaluronic acid (HA) (sCT-HA) with high association efficiency up to 96.84 ± 7.25%. This composite hydrogel showed a tunable biodegradable property. In vitro sCT release profiles revealed that this hydrogel can achieve long-term sustained sCT release (28 days) with considerable structure stability. The cellular study illustrated outstanding compatibility and osteoconductive potential of this multi-component hydrogel according to the higher ALP activity (2.10-fold), calcium expression (2.30-fold) and extracellular calcium deposition (1.10-fold) compared to that of the sCT group. In vivo sCT release confirmed that this hydrogel system realized sustained sCT release and a continuous hypocalcemic effect for as long as 28 days, and there were no inflammation and immune responses according to the histological evaluations (H&E and IgG staining). These findings demonstrate that this osteoconductive hydrogel system can provide a promising method for therapy of bone related disease.

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