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1.
Stem Cell Res Ther ; 10(1): 279, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470890

RESUMO

OBJECTIVE: Autograft microskin transplantation has been widely used as a skin graft therapy in full-thickness skin defect. However, skin grafting failure can lead to a pathological delay wound healing due to a poor vascularization bed. Considering the active role of adipose-derived stem cell (ADSC) in promoting angiogenesis, we intend to investigate the efficacy of autograft microskin combined with ADSC transplantation for facilitating wound healing in a full-thickness skin defect mouse model. MATERIAL AND METHODS: An in vivo full-thickness skin defect mouse model was used to evaluate the contribution of transplantation microskin and ADSC in wound healing. The angiogenesis was detected by immunohistochemistry staining. In vitro paracrine signaling pathway was evaluated by protein array and Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis. RESULTS: Co-transplantation of microskin and ADSC potentiated the wound healing with better epithelization, smaller scar thickness, and higher angiogenesis (CD31) in the subcutaneous layer. We found both EGF and VEGF cytokines were secreted by microskin in vitro. Additionally, secretome proteomic analysis in a co-culture system of microskin and ADSC revealed that ADSC could secrete a wide range of important molecules to form a reacting network with microskin, including VEGF, IL-6, EGF, uPAR, MCP-3, G-CSF, and Tie-2, which most likely supported the angiogenesis effect as observed. CONCLUSION: Overall, we concluded that the use of ADSC partially modulates microskin function and enhances wound healing by promoting angiogenesis in a full-thickness skin defect mouse model.

2.
J Neuromuscul Dis ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31498126

RESUMO

Calpainopathy, also known as limb girdle muscular dystrophy (LGMD) type 2A (LGMD2A) or LGMD R1 Calpain3-related, is one of the most common genetically characterized forms of limb-girdle muscular dystrophy with a wide range of phenotypic severity. We evaluated a consanguineous family with a clinical phenotype consistent with calpainopathy in whom conventional sequencing did not detect any mutations in the CAPN3 gene. Using whole exome sequencing paired with haplotype analysis, we identified a homozygous deep intronic single base pair deletion in CAPN3 (c.946-29delT). Familial segregation studies were consistent with recessive inheritance. Immunoblotting of muscle tissue from the patient showed complete absence of calpain 3. In silico analysis predicted the deletion to disrupt the branch point and subsequently alter splicing of exon 7. Studies of patient fibroblasts and muscle tissue confirmed altered splicing, resulting in an inclusion of a 389-bp intronic sequence upstream of exon 7, originating from a cryptic splice acceptor site in intron 6. This out-of-frame insertion results in a premature stop codon, leading to an apparent absence of protein likely due to degradation of the transcript via nonsense-mediated decay. We then designed phosophorodiamidate morpholino oligomers (PMOs) as splice modulators to block the new splice acceptor site. This approach successfully prevented the aberrant splicing - reverting the majority of the splice to the wildtype transcript. These results confirm the pathogenicity of this novel deep intronic mutation and provide a mutation-specific therapeutic strategy. Thus, deep intronic mutations in CAPN3 may be pathogenic and should be considered in the appropriate clinical setting. The identification of mutations which may be missed by traditional Sanger sequencing is essential as they may be excellent targets for individualized therapeutic strategies using RNA-directed splice modulation.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31509352

RESUMO

OBJECTIVE: To characterize the natural history and clinical features of myopathies caused by mono-allelic, dominantly acting pathogenic variants in COL12A1. METHODS: Patients with dominant COL12A1-related myopathies were characterized by history and clinical examination, muscle imaging, and genetic analysis. Pathogenicity of the variants was assessed by immunostaining patient-derived dermal fibroblast cultures for collagen XII. RESULTS: Four independent families with childhood-onset weakness due to novel, dominantly acting pathogenic variants in COL12A1 were identified. Adult patients exhibited distal-predominant weakness. Three families carried dominantly acting glycine missense variants, and one family had a heterozygous, intragenic, in-frame deletion of exon 52 of COL12A1. All pathogenic variants resulted in increased intracellular retention of collagen XII in patient-derived fibroblasts as well as loss of extracellular, fibrillar collagen XII deposition. Since haploinsufficiency for COL12A1 is largely clinically asymptomatic, we designed and evaluated small interfering RNAs (siRNAs) that specifically target the mutant allele containing the exon 52 deletion. Immunostaining of the patient fibroblasts treated with the siRNA showed a near complete correction of collagen XII staining patterns. INTERPRETATION: This study characterizes a distal myopathy phenotype in adults with dominant COL12A1 pathogenic variants, further defining the phenotypic spectrum and natural history of COL12A1-related myopathies. This work also provides proof of concept of a precision medicine treatment approach by proposing and validating allele-specific knockdown using siRNAs specifically designed to target a patient's dominant COL12A1 disease allele.

4.
Biofactors ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31518024

RESUMO

Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABAA R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with alcoholism did induce a status like alcohol dependence in C57BL/6J mice. The decreased expression of BDNF, α1GABAA R, and mGluR1/ PKC ε may be the underlying mechanism.

5.
PLoS Genet ; 15(9): e1008272, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31513573

RESUMO

Newly emerged wheat blast disease is a serious threat to global wheat production. Wheat blast is caused by a distinct, exceptionally diverse lineage of the fungus causing rice blast disease. Through sequencing a recent field isolate, we report a reference genome that includes seven core chromosomes and mini-chromosome sequences that harbor effector genes normally found on ends of core chromosomes in other strains. No mini-chromosomes were observed in an early field strain, and at least two from another isolate each contain different effector genes and core chromosome end sequences. The mini-chromosome is enriched in transposons occurring most frequently at core chromosome ends. Additionally, transposons in mini-chromosomes lack the characteristic signature for inactivation by repeat-induced point (RIP) mutation genome defenses. Our results, collectively, indicate that dispensable mini-chromosomes and core chromosomes undergo divergent evolutionary trajectories, and mini-chromosomes and core chromosome ends are coupled as a mobile, fast-evolving effector compartment in the wheat pathogen genome.

6.
Food Res Int ; 124: 86-92, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31466654

RESUMO

This study aimed at producing isomaltooligosaccharides in juice blends using orange juice and malt extract and assessing their acceptability. Different blend formulations were prepared and fermented, varying the concentration of orange juice, sucrose and malt extract. Dextransucrase from Weissella cibaria 10 M was used to enzymatically synthesize α(1-6) linked glucan-oligosaccharides by transglycosylation reactions, with maltose as acceptor carbohydrate and sucrose as donor. The optimal yield of oligosaccharides was after 24 h, producing 19.4 g/L of oligosaccharides (degree of polymerization 3) from 36 g/L maltose and 19 g/L sucrose. All the blend proved to be good alternatives for synthesizing isomalto-oligosaccharides with different degrees of polymerization. Sensory analysis showed good average acceptability compared to natural orange juice, achieving scores of around 6 on a 9-point hedonic scale. In a comprehensive analysis, juice blends containing orange juice and malt extract with Weissella cibaria to produce oligosaccharides exhibited good sensory indicators as an innovative prebiotic beverage. A prebiotic oligosaccharide beverage can be produced by enzymatic synthesis of oligosaccharides with different degrees of polymerization.

7.
Epidemiol Infect ; 147: e192, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31364532

RESUMO

Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a major cause of community-acquired pneumonia in China. Data on epidemiology of paediatric MPP from China are little known. This study retrospectively collected data from June 2006 to June 2016 in Beijing Children's Hospital, Capital Medical University of North China and aims to explore the epidemiological features of paediatric MPP and severe MPP (SMPP) in North China during the past 10 years. A total of 27 498 paediatric patients with pneumonia were enrolled. Among them, 37.5% of paediatric patients had MPP. In this area, an epidemic took place every 2-3 years at the peak, and the positive rate of MPP increased during these peak years over time. The peak age of MPP was between the ages of 6 and 10 years, accounting for 75.2%, significantly more compared with other age groups (χ2 = 1384.1, P < 0.0001). The epidemics peaked in September, October and November (χ2 = 904.9, P < 0.0001). Additionally, 13.0% of MPP paediatric patients were SMPP, but over time, the rate of SMPP increased, reaching 42.6% in 2016. The mean age of paediatric patients with SMPP (6.7 ± 3.0 years old) was younger than that of patients with non-SMPP (7.4 ± 3.2 years old) (t = 3.60, P = 0.0001). The prevalence of MPP and SMPP is common in China, especially in children from 6 to 10 years old. Paediatric patients with SMPP tend to be younger than those with non-SMPP. MPP outbreaks occur every 2-3 years in North China. September, October and November are the peak months, unlike in South China. Understanding the epidemiological characteristics of paediatric MPP can contribute to timely treatment and diagnosis, and may improve the prognosis of children with SMPP.

8.
J Cancer Res Ther ; 15(4): 921-926, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31436253

RESUMO

Aims: ATP-binding cassette subfamily C member 3 (ABCC3) is involved in multidrug resistance and is overexpressed in some solid tumors. Recent work revealed an increase in circulating anti-ABCC3 antibodies in lung and esophageal cancers. This in vitro study was undertaken to investigate the effects of the natural IgG antibody against the ABCC3-derived peptide antigen on proliferation of oral squamous cell carcinoma (OSCC) cells and augment the development of efficient and effective treatments in patients with OSCC. Subjects and Methods: An in-house enzyme-linked immunosorbent assay was applied to detect anti-ABCC3 IgG antibody in human plasma. Two OSCC cell lines, CAL27 and SCC15, were cultured with 20% plasma either positive or negative for anti-ABCC3 IgG. Cell proliferation was quantified by the CCK-8 method, and cell apoptosis and cell cycle distribution were analyzed by flow cytometry. The expression of the ABCC3 gene in the cell lines was analyzed by reverse transcriptase quantitative real-time polymerase chain reaction. Results: The results showed that plasma anti-ABCC3 IgG significantly inhibited the proliferation of CAL27 cells but not SCC15 cells, although ABCC3 was expressed in both cell lines. The proportion of apoptotic cells was significantly higher in CAL27 cells treated with anti-ABCC3 IgG-positive plasma than in those treated with IgG-negative plasma. Cell cycle progression was arrested in CAL27 cells treated with anti-ABCC3 IgG-positive plasma. Conclusions: Our data suggest that human plasma anti-ABCC3 IgG may be a promising agent in anti-OSCC therapy, although further studies are needed to arrive at a definitive conclusion.

9.
Biomed Pharmacother ; 118: 109279, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31376651

RESUMO

COX-2 specific inhibitor, which has been widely used, can delay bone fracture healing and reduce osteogenic potential of bone marrow stromal cells. However, it remains unknown how to prevent these side-effects of COX-2 inhibitor. In this study, we introduced BMP9-induced osteogenic differentiation as model to evaluate whether all-trans retinoic acid (ATRA) could ameliorate these adverse effects of COX-2 specific inhibitor on bone metabolism with in vitro and in vivo experiments, and uncover the possible mechanism underlying this process. Results showed that ATRA enhanced the potential of BMP9 to induce the osteogenic markers, such as alkaline phosphates (ALP) and mineralization; but retinoic acid receptor a (RARa) inhibitor showed the reversal effects. COX-2 specific inhibitor (NS398) reduced the osteogenic markers induced by BMP9, and ATRA almost eliminated the inhibitory effect of NS398. BMP9 up-regulated the protein level of ß-catenin and promoted it translocate to nucleus, and both were reduced by NS398. On the contrary, ATRA notablely attenuated the inhibitory effect of NS398 on BMP9-increased ß-catenin. Exogenous RXRa obviously ameliorated the inhibitory effect of silencing COX-2 on ectopic bone formation induced by BMP9. NS398 reduced the level of phosphorylated CREB, which was almost reversed by ATRA. Besides, RXRa interacted with phosphorylated CREB directly and both were recruited at ß-catenin promoter region. Thus, we demonstrated that ATRA may reverse the side-effects of COX-2 inhibitor on bone metabolism through increasing the activation of Wnt/ß-catenin pathway partly.

10.
Nanoscale ; 11(35): 16476-16487, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31453622

RESUMO

Pancreatic cancer is a highly malignant carcinoma with limited effective treatment options, resulting in a poor patient survival rate of less than 5%. In this study, cationic albumin nanoparticles were assembled with negatively charged hyaluronic acid (HA) to achieve a hierarchical nanostructure and efficient delivery of small molecule drugs to the tumor site in the pancreas. A combination of chemotherapy with indoleamine-2,3-dioxygenase (IDO) inhibition was explored to enhance the chemotherapeutic efficacy in vivo. Hydrophobic celastrol (CLT) and hydrophilic 1-methyltryptophan (MT) were concurrently loaded in HA coated cationic albumin nanoparticles (HNPs) with an average size of ∼300 nm. The size of HNPs was reduced in the presence of hyaluronidase to facilitate penetration into deep tumor tissues. Also, the biodistribution study in the C57BL/6 mice xenograft model showed enhanced tumor accumulation and prolonged circulation of HNPs. Compared with CLT solution, the combination of CLT with MT showed significantly enhanced tumor inhibition in both xenograft and orthotopic pancreatic cancer mice models via downregulating the immunosuppressive tumor microenvironment. Taken together, the combination of CLT with MT administered via HNPs represents a highly promising strategy for targeted pancreatic cancer therapy.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31411917

RESUMO

Activation of calpain1 (CPN1) and calpain2 (CPN2) contributes to cardiac injury during ischemia (ISC) and reperfusion (REP). Complex I activity is decreased in heart mitochondria following ISC-REP. CPN1 and CPN2 are ubiquitous calpains that exist in both cytosol (cs-CPN1&2) and mitochondria (mit-CPN1&2). Recent work shows that the complex I subunit (NDUFS7) is a potential substrate of the mit-CPN1. We asked if ISC-REP led to decreased complex I activity via proteolysis of the NDUFS7 subunit via activation of mit-CPN1&2. Activation of cs-CPN1&2 decreases mitophagy in hepatocytes following ISC-REP. We asked if activation of cs-CPN1&2 impaired mitophagy in the heart following ISC-REP. Buffer-perfused rat hearts underwent 25 min. global ISC and 30 min. REP. MDL-28170 (MDL, 10 µM) was used to inhibit CPN1&2. Cytosol, subsarcolemmal mitochondria (SSM), and interfibrillar mitochondria (IFM) were isolated at the end of heart perfusion. Cardiac ISC-REP led to decreased complex I activity with a decrease in the content of NDUFS7 in both SSM and IFM. ISC-REP also resulted in a decrease in cytosolic beclin1 content, a key component of the autophagy pathway required to form autophagosomes. MDL treatment protected the contents of cytosolic beclin1 and mitochondrial NDUFS7 in hearts following ISC-REP. These results support that activation of both cytosolic and mitochondrial calpains impairs mitochondria during cardiac ISC-REP. Mitochondria localized calpains impair complex I via cleavage of a key subunit. Activation of cytosolic calpains contributes to mitochondrial dysfunction by impairing removal of the impaired mitochondria through depletion of a key component of the mitophagy process.

12.
Comput Assist Surg (Abingdon) ; : 1-7, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31448960

RESUMO

Percutaneous needle puncture operation is widely used in the image-guided interventions, including biopsy and ablation. MRI guidance has the advantages of high-resolution soft tissue imaging and thermal monitoring during energy-based ablation. This paper proposes the design of a 5-DOF pneumatic needle puncture robot, with all the cylinders, sensors and structure material MRI-compatible. Also, a hybrid fuzzy-PID controller is designed for the pneumatic driven system to adjust the PID parameters adaptively. The experiment validation result shows that, compared with the traditional fix-parameter PID control, the proposed hybrid fuzzy-PID control has no overshoot, and the settle time/steady state error remains low even with increasing load. This proves that the hybrid fuzzy-PID control strategy can increases the positioning accuracy and robustness of the pneumatic driven needle puncture robot, which is significant for the safety of percutaneous needle puncture operation.

13.
Neurol India ; 67(3): 829-833, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347562

RESUMO

Purpose: To explore the optimal postlabeling delay (PLD) of arterial spin labeling (ASL) in different age groups and the correlation between cerebral blood flow (CBF) and age in adults. Materials and Methods: Eighty-four healthy adults (20-80 years) were divided into three groups (youth group, middle-aged group, elderly group) and underwent conventional MRI and three-dimensional arterial spin labeling (3D-ASL) perfusion scanning. Multi-phase PLDs (1025,1525, 2525, 3025ms) were used in each age group. Statistical parametric mapping (SPM) was used to analyze the data and to extract the CBF of predefined regions of interest (ROI) including whole brain gray matter, frontal lobe, parietal lobe, temporal lobe, occipital lobe and limbic lobe. Results: The CBF of shorter PLDs (1025,1525ms) were higher in the youth group, and the CBF were higher with longer PLDs (2525,3025ms) in the middle-aged and elderly group. In addition, the standard deviation of CBF was lower with longer PLD in all age groups. The CBF of all ROIs had negative correlation with age (r=-0.440, P < 0.001; -0.425, P < 0.001; -0.412, P < 0.001; -0.553, P < 0.001; -0.464, P < 0.001; -0.450, P < 0.001 for each ROIs respectively). The youth and middle-aged group, the youth and elderly group had statistically significant difference (P < 0.05); however, the middle-aged and elderly group had no difference (P > 0.05). Conclusion: The shorter PLD is suitable for the youth group and 1525 ms is the best PLD. The longer PLD is suitable for the middle-aged group and elderly group and 3025ms is the best PLD. Most brain regional CBF parameters decrease with age and gradually reach a plateau after middle age.

14.
JAMA Netw Open ; 2(7): e197621, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31339548

RESUMO

Importance: There are a limited number of predictive biomarkers for hyperprogressive disease (HPD), which is induced by immune checkpoint blockade (ICB) therapy. Objective: To evaluate the association of biomarkers in serum with the response to ICB therapy in patients with metastatic gastrointestinal tract cancer. Design, Setting, and Participants: Cohort study in which patients with metastatic gastrointestinal tract cancer treated with ICB were enrolled at the Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China, from August 1, 2015, to July 31, 2017, with the last follow-up date on January 1, 2018. Serum samples were collected at baseline and during the first visit to the clinic after starting treatment. Data analysis was conducted from January 16, 2018, to September 1, 2018. Exposures: A total of 59 factors, including cytokines/chemokines, growth factors, and soluble checkpoint-related proteins in serum, were examined by multiplexed bead immunoassays. Main Outcomes and Measures: Tree-based estimators were used to evaluate the importance of serum protein levels to ICB treatment response. Progression-free survival and overall survival analyses were conducted with the Kaplan-Meier method and log-rank test. Results: In total, 56 patients were examined. All patients with HPD (5 [8.9%]) had significantly lower mean (SD) levels of serum monocyte chemoattractant protein 1 than patients without HPD at baseline (53.4 [17.3] pg/mL vs 106.4 [48.4] pg/mL; P = .02). All patients with HPD were also identified by lower leukemia inhibitory factor levels (<13.28 pg/mL) and higher cluster of differentiation 152 levels (≥31.81 pg/mL). Among the remaining 51 patients, responders with esophageal squamous cell carcinoma (ESCC) or colorectal cancer (CRC) showed larger decreases in interleukin 1 receptor antagonist levels than nonresponders (ESCC: -55.02% [95% CI, -86.52% to -23.51%] vs 43.44% [95% CI, 11.93% to 74.96%]; P < .001; CRC: -35.82% [95% CI, -67.38% to -4.26%] vs 59.14% [95% CI, -72.34% to 190.6%]; P = .04). Responders with gastric cancer (GC) had larger increases in brain-derived neurotrophic factor levels than nonresponders (44.77% [95% CI, 10.76% to 78.79%] vs -26.2% [95% CI, -58.53% to 6.12%]; P = .003). Furthermore, early decreases in serum interleukin 1 receptor antagonist in patients with metastatic ESCC and CRC were associated with longer progression-free survival (ESCC: not reached vs 2.1 months; hazard ratio, 0.19; 95% CI, 0.04 to 0.95; P = .04; CRC: not reached vs 2.1 months; hazard ratio, 0.06; 95% CI, 0.01 to 0.38; P < .001). Early increases in brain-derived neurotrophic factor levels in patients with metastatic GC were associated with longer progression-free survival (not reached vs 4.2 months; hazard ratio, 0.15; 95% CI, 0.03 to 0.84; P = .03). Conclusions and Relevance: In this study, baseline serum levels of monocyte chemoattractant protein 1, leukemia inhibitory factor, and cluster of differentiation 152 were associated with hyperprogressive metastatic gastrointestinal cancer among patients receiving ICB. An early decrease in serum interleukin 1 receptor antagonist levels in patients with metastatic ESCC or CRC and an early increase in serum brain-derived neurotrophic factor levels in patients with metastatic GC were better able to identify who would respond to ICB compared with microsatellite stability status or programmed cell death ligand 1 expression.

15.
Bioessays ; 41(8): e1900008, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31270822

RESUMO

l-Lactate is emerging as a crucial regulatory nexus for energy metabolism in the brain and signaling transduction in synaptic plasticity, memory processes, and drug addiction instead of being merely a waste by-product of anaerobic glycolysis. In this review, the role of lactate in various memory processes, synapse plasticity and drug addiction on the basis of recent studies is summarized and discussed. To this end, three main parts are presented: first, lactate as an energy substrate in energy metabolism of the brain is described; second, lactate as a novel signaling molecule in synaptic plasticity, neural circuits, memory, and drug addiction is described; and third, in light of the above descriptions, it is plausible to speculate that lactate is predominantly a signaling molecule in specific memory processes and partly acts as an energy substrate. The future perspective in lactate signaling involving microglia and associated precise signaling pathways in the brain is highlighted.

16.
Carbohydr Polym ; 222: 115017, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320078

RESUMO

Water purification has always being an imperative but challenging issue of our times. Here, we used an organic-inorganic material, i.e. bacterial cellulose (BC) and Ca-montmorillonite (Ca-MMT) composites to treat complex wastewater. The surface and inside of the BC/Ca-MMT was a microporous structure capable of providing abundant adsorption sites. We demonstrated the BC/Ca-MMT has superior removal efficiency towards methylene blue (MB) and tetracycline (TC). Typically, the sample showed significant uptake ability towards MB and TC with uptake characteristics of pseudo-second-order model and Langmuir isotherm model. More interestingly, in MB-TC binary system, the removal of the two contaminative species was hardly affected by other coexisting components. Meanwhile, the sample was ease of regeneration and kept stable reusability through consecutive four recycles. With more virtues, such as low cost and wide range of resources of the two raw materials, the BC/Ca-MMT is expected to be a promising versatile water purifier in sewage treatment.

17.
Protein Cell ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31321704

RESUMO

Accelerated forgetting has been identified as a feature of Alzheimer's disease (AD), but the therapeutic efficacy of the manipulation of biological mechanisms of forgetting has not been assessed in AD animal models. Ras-related C3 botulinum toxin substrate 1 (Rac1), a small GTPase, has been shown to regulate active forgetting in Drosophila and mice. Here, we showed that Rac1 activity is aberrantly elevated in the hippocampal tissues of AD patients and AD animal models. Moreover, amyloid-beta 42 could induce Rac1 activation in cultured cells. The elevation of Rac1 activity not only accelerated 6-hour spatial memory decay in 3-month-old APP/PS1 mice, but also significantly contributed to severe memory loss in aged APP/PS1 mice. A similar age-dependent Rac1 activity-based memory loss was also observed in an AD fly model. Moreover, inhibition of Rac1 activity could ameliorate cognitive defects and synaptic plasticity in AD animal models. Finally, two novel compounds, identified through behavioral screening of a randomly selected pool of brain permeable small molecules for their positive effect in rescuing memory loss in both fly and mouse models, were found to be capable of inhibiting Rac1 activity. Thus, multiple lines of evidence corroborate in supporting the idea that inhibition of Rac1 activity is effective for treating AD-related memory loss.

18.
Medicine (Baltimore) ; 98(26): e16166, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261546

RESUMO

RATIONALE: The placenta membranacea (PM) is a rare type of placental abnormality, which is associated with placenta previa, antepartum hemorrhage (APH), postpartum hemorrhage (PPH), chorioamnionitis, fetal growth restriction (FGR), preterm birth even stillbirth. The purpose of this case report is to summarize the characteristics and analyze the relevant factors of PM. PATIENTS CONCERNS: Repetitive B-ultrasound of the first patient demonstrated a thin placenta covering the most part of uterine wall, which completely covers the internal cervical ostium for 22 weeks. B-ultrasound of the second patient showed placenta partially covering the internal cervical ostium and fetus small for gestation age for 23 days. The third patient complained of abdominal pain and vaginal discharge for 1 day. DIAGNOSES: Diagnosis of PM is based on Doppler ultrasound apparatus, and confirmed by pathology. INTERVENTIONS AND OUTCOMES: In the first patient, elective cesarean section was performed. The second patient required termination of pregnancy due to poor postnatal outcome. The third patient underwent intrauterine fetal death. Of these 3 cases, one delivered a term fetus by cesarean section complicated with placenta previa and placenta accreta, one terminated the pregnancy because of serious fetal growth retardation, and the other underwent intrauterine fetal death. LESSONS: High-resolution color Doppler ultrasound apparatus can improve the diagnostic accuracy, and close antenatal surveillance followed by proper arrangement of delivery may improve neonatal outcomes.


Assuntos
Placenta/anormalidades , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Placenta/diagnóstico por imagem , Placenta/patologia , Gravidez , Resultado da Gravidez , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-Natal , Adulto Jovem
19.
Int J Biol Sci ; 15(7): 1358-1367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337967

RESUMO

Triple negative breast cancer (TNBC) is a highly aggressive cancer and lack of targeting therapies. It is believed that the breast cancer stem cells (BCSCs) are responsible for the aggressive characteristics of TNBC. Hence, developing BCSC-targeting agents may provide new therapeutic strategies for the patients. Huaier polysaccharide (HP), an active ingredient extracted from the mushroom Trametes robiniophila Murr, has been widely used in clinical anti-cancer treatments in China. Here we demonstrated that HP could target BCSCs in TNBC cells, resulting in decreased mammosphere formation, downregulated expression of stem-related genes and reduced proportion of aldehyde dehydrogenase positive cells in vitro, and inhibited xenograft tumor formation in vivo. Mechanically, HP markedly reduced the expression of estrogen receptor α-36 (ERα-36), a recently identified subtype of estrogen receptor α, and attenuated ERα-36-mediated activation of AKT/ß-catenin signaling in ERα-36high TNBC cells. This study provides a new insight into the mechanism of HP on BCSC-targeting therapy and new ideas for comprehensive treatment strategies for TNBC.

20.
Eur J Pharmacol ; 861: 172556, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31325436

RESUMO

Glioma is one of the most universally diagnosed malignant tumors in the central nervous system with high mortality and morbidity in the world. Long non-coding long intergenic non-protein coding RNA 319 (LINC00319) exerts promoting function in diverse range of human carcinomas, but its detailed role in glioma remains to be investigated. This study aimed to investigate the potential role and regulatory mechanism of LINC00319 and also its clinical value in glioma. In our study, LINC00319 was expressed at high levels in glioma and closely associated with poor prognosis of patients with glioma, whose knockdown impaired cell proliferation, arrested cell cycle and induced cell apoptosis of glioma. In addition, high expression of high mobility group AT-hook 2 (HMGA2) was found in glioma which was also in positive relation to LINC00319 expression. Moreover, LINC00319 directly bound to TATA-box binding protein associated factor 1 (TAF1) and further regulated HMGA2. Finally, rescue assays verified that LIN00319 modulated the tumorigenesis of glioma by regulating HMGA2. The present research elucidated the function role and underlying mechanism of LINC00319 in glioma and exposed a new insight into the molecular-targeted therapy for glioma.

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