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1.
J Hazard Mater ; 383: 121123, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31520937

RESUMO

This work presents the first fabrication of smart nonwoven fabric (DSR-CZPP) with extraordinary reversible double-stimulus responsive wettability, where carboxyl groups of cellulose nanocrystals/zinc oxide (CNC/ZnO) nanohybrids deposited on fabric surface can bond with hydroxyl group of the PDMAEMA-b-PHEMA-b-PMAAAB triblock polymer brushes that was prepared by using methyl methacrylate (HEMA), dimethylaminoethyl methacrylate (DMAEMA) and methacrylamide-azobenzene monomer (MAAAB) via reversible addition-fragmentation chain transfer (RAFT). The peculiar reversible double-stimulus responsive wettability of the DSR-CZPP can be modulated by triggering hydrophilic/hydrophobic transitions and lipophilic/oleophobic transitions under dual-stimulations of pH and UV light irradiation. The special molecular structure of the triblock polymer brushes enabled DSR-CZPP to intelligent modulation of oil-water separation under the control of "UV & pH double switch", meanwhile CNC/ZnO simultaneously can induce the photocatalytic degradation of organic dyes. Moreover, DSR-CZPP can have high removal ratios of various pollutants, such as metal ion (Cu2+) and toxic organic solvent (silicone oil, acetone and chloroform). This smart and multifunctional fabric shows great potentials for treating complicated polluted water from most industrial fields.

2.
Clin Neurol Neurosurg ; 187: 105573, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706107

RESUMO

OBJECTIVE: Advanced techniques such as volumetric-modulated arc therapy (VMAT) may reduce radiation damage and improve the quality of life for patients.We performed a study comparing dose distributions to the planning target volumes(PTVs) and other organs at risk (OARs) of intensity-modulated radiotherapy (IMRT),coplanar VMAT (coVMAT), and non-coplanar VMAT (ncVMAT). PATIENTS AND METHODS: 13 patients with GBM who had undergone postoperative radiotherapy were enrolled. Three plans for each patient were created, namely, IMRT, coVMAT, and ncVMAT. Prescription doses and normal-tissue constraints were identical for these three plans. The dosimetric differences of target dose distribution, conformity index (CI), homogeneity index (HI), the gradient index (GI), dose of OARs, monitor units (MUs) and beam-on times among these three plans were investigated. RESULTS: These three techniques resulted in comparable maximum, minimum, and mean PTV doses. Small but insignificant differences were observed in GI,CI, and HI. Compared with IMRT, VMAT plans showed statistically significant reductions in the mean doses to the optic chiasm (P < 0.05). Compared with IMRT, VMAT techniques significantly reduced the number of MUs and less beam-on time than IMRT techniques (P < 0.05). However, calculation times were significantly longer for ncVMAT and coVMAT plans at 12 and 12.3 min, versus 2.6 min for IMRT. Our study showed that IMRT or VMAT planning is feasible and efficient for patients with GBM.Compared to IMRT plans, ncVMAT or coVMAT plans showed similar PTV coverage and comparable OARs sparing. VMAT plans significantly reduces the mean doses to the optic chiasm than IMRT plans. CONCLUSION: There was no obvious superiority of ncVMAT over coVMAT in target coverage and sparing of OARs.Compared with IMRT, VMAT techniques significantly reduced the number of MUs and beam-on time but extended the calculation times.

3.
Clin Rheumatol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713733

RESUMO

OBJECTIVE: To assess the efficacy and safety of the Chinese herb Tripterygium wilfordii Hook F (TwHF) for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: SSc-ILD patients who were regularly treated for more than 1 year and were currently taking a stable dose of TwHF (40-60 mg/day) or CYC (100 mg/day) were selected from the EUSTAR database of Peking Union Medical College Hospital. The efficacy of treatments was assessed by the change in pulmonary function, including the forced vital capacity (FVC) and the percentage of predicted FVC (FVC pred%). RESULTS: Among the 431 patients diagnosed with SSc-ILD, 76 fulfilled the inclusion and exclusion criteria. Twenty eight patients received TwHF monotherapy, while 48 received oral CYC monotherapy. Baseline data prior to treatment did not differ significantly between the two groups. After 1 year of treatment, significant improvements in the FVC and FVC pred% were seen in both groups (P < 0.05) and the magnitude of improvement was comparable (P = 0.93). However, TwHF was only found to be effective in improving FVC and FVC pred% when administered as a maintenance therapy, but not as an induction therapy. No severe adverse events were seen in either group. Leucopenia occurred more often in the CYC group compared to the TwHF group (P = 0.034). CONCLUSION: TwHF may be considered as a potential alternative drug for SSc-ILD patients, especially as a maintenance therapy. A prospective randomized controlled trial is necessary to further confirm these results.Key Points• This is the first clinical study of Tripterygium wilfordii Hook F (TwHF) in the treatment of SSc-ILD, providing a novel therapeutic option for SSc-ILD.• TwHF shows a comparable therapeutic efficacy to CYC when treating SSc-ILD.• TwHF has unique therapeutic advantages considering the balance of economy and safety and may be a good potential choice for maintenance therapy.

4.
ACS Appl Mater Interfaces ; 11(47): 44642-44651, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31684724

RESUMO

Electronic skins are developed for applications such as biomedical sensors, robotic prosthetics, and human-machine interactions, which raise the interest in composite materials that possess both flexibility and sensing properties. Polypyrrole-coated cellulose nanocrystals and cellulose nanofibers were prepared using iron(III) chloride (FeCl3) oxidant, which were used to reinforce polyvinyl alcohol (PVA). The combination of weak H-bonds and iron coordination bonds and the synergistic effect of these components yielded self-healing nanocomposite films with robust mechanical strength (409% increase compared to pure PVA and high toughness up to 407.1%) and excellent adhesion (9670 times greater than its own weight) to various substrates in air and water. When damaged, the nanocomposite films displayed good mechanical (72.0-76.3%) and conductive (54.9-91.2%) recovery after a healing time of 30 min. More importantly, the flexible nanocomposites possessed high strain sensitivity under subtle strains (<48.5%) with a gauge factor (GF) of 2.52, which was relatively larger than the GF of ionic hydrogel-based skin sensors. These nanocomposite films possessed superior sensing performance for real-time monitoring of large and subtle human motions (finger bending motions, swallowing, and wrist pulse); thus, they have great potentials in health monitoring, smart flexible skin sensors. and wearable electronic devices.

5.
J Autoimmun ; : 102336, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31601476

RESUMO

Excessive inflammatory cytokines play crucial roles in the pathogenesis of rheumatoid arthritis (RA), however, the underlying mechanism remains unclear. In this study, we demonstrated that pentaxin 3 (PTX3), an essential component of innate immunity, was elevated in RA and preferentially bound to CD14+ monocytes. C1q promoted the binding and resulted in increased cell proliferation, activation and caspase-1-related late apoptotic cells (7-AAD+annexin V+), as well as enhanced release of inflammatory cytokines including TNF-α, IL-1ß and IL-6. Serum from RA patients, compared with healthy controls, induced gasdermin D (GSDMD)-dependent pyroptosis in monocytes, and this ability was associated with disease activity. Moreover, PTX3 synergized with C1q to promote pyroptosis in RA-serum pre-incubated monocytes by coordinately enhancing NLRP3 inflammasome over-activation and inducing GSDMD cleavage, cell swelling with large bubbles, caspase-1-dependent cell death and inflammatory cytokine release including IL-6. On the other hand, IL-6 promoted PTX3 plus C1q-induced pyroptosis in both normal and RA serum pre-incubated monocytes. These findings collectively implicated an important role of IL-6 in driving PTX3 plus C1q-mediated pyroptosis in RA and shed lights on a potential new treatment strategy targeting pyroptosis-mediated persistent inflammatory cytokine release.

6.
Glob Chang Biol ; 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31495039

RESUMO

Recycling of livestock manure to agricultural land may reduce the use of synthetic fertilizer and thereby enhance the sustainability of food production. However, the effects of substitution of fertilizer by manure on crop yield, nitrogen use efficiency (NUE), and emissions of ammonia (NH3 ), nitrous oxide (N2 O) and methane (CH4 ) as function of soil and manure properties, experimental duration and application strategies have not been quantified systematically and convincingly yet. Here, we present a meta-analysis of these effects using results of 143 published studies in China. Results indicate that the partial substitution of synthetic fertilizers by manure significantly increased the yield by 6.6% and 3.3% for upland crop and paddy rice, respectively, but full substitution significantly decreased yields (by 9.6% and 4.1%). The response of crop yields to manure substitution varied with soil pH and experimental durations, with relatively large positive responses in acidic soils and long-term experiments. NUE increased significantly at a moderate ratio (<40%) of substitution. NH3 emissions were significantly lower with full substitution (62%-77%), but not with partial substitution. Emissions of CH4 from paddy rice significantly increased with substitution ratio (SR), and varied by application rates and manure types, but N2 O emissions decreased. The SR did not significantly influence N2 O emissions from upland soils, and a relative scarcity of data on certain manure characteristic was found to hamper identification of the mechanisms. We derived overall mean N2 O emission factors (EF) of 0.56% and 0.17%, as well as NH3 EFs of 11.1% and 6.5% for the manure N applied to upland and paddy soils, respectively. Our study shows that partial substitution of fertilizer by manure can increase crop yields, and decrease emissions of NH3 and N2 O, but depending on site-specific conditions. Manure addition to paddy rice soils is recommended only if abatement strategies for CH4 emissions are also implemented.

7.
EBioMedicine ; 47: 373-383, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492563

RESUMO

BACKGROUND: The gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development. METHOD: We used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naïve type 2 diabetic (TN-T2D, n = 77), pre-diabetic (Pre-DM, n = 80), and normal glucose tolerant (NGT, n = 97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naïve T2D individuals to elucidate possible host-microbial interplays characterizing different disease stages. FINDINGS: We observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups. INTERPRETATION: Our findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and point to the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host. FUND: The study was supported by the National Natural Science Foundation of China (No. 31601073), the National Key Research and Development Program of China (No. 2017YFC0909703) and the Shenzhen Municipal Government of China (No. JCYJ20170817145809215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

8.
Int J Nanomedicine ; 14: 6601-6613, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496701

RESUMO

Purpose: The primary goal of the present study was to explore and evaluate the highly conserved Neisserial surface protein A (NspA) molecule, fused with truncated HBV virus-like particles (VLPs), as a candidate vaccine against the virulent Neisseria meningitidis serogroup B (NMB). Methods: NspA was inserted into the major immunodominant region of the truncated hepatitis B virus core protein (HBc; amino acids 1-144). The chimeric protein, HBc-N144-NspA, was expressed from a prokaryotic vector and generated HBc-like particles, as determined by transmission electron microscopy. Further, the chimeric protein and control proteins were used to immunize mice and the resulting immune responses evaluated by flow cytometry, enzyme-linked immunosorbent assay, and analysis of serum bactericidal activity (SBA) titer. Results: Evaluation of the immunogenicity of the recombinant HBc-N144-NspA protein showed that it elicited the production of high levels of NspA-specific total IgG. The SBA titer of HBc-N144-NspA/F reached 1:16 2 weeks after the last immunization in BALB/c mice, when human serum complement was included in the vaccine. Immunization of HBc-N144-NspA, even without adjuvant, induced high levels of IL-4 and a high IgG1 to IgG2a ratio, confirming induction of an intense Th2 immune response. Levels of IL-17A increased rapidly in mice after the first immunization with HBc-N144-NspA, indicating the potential for this vaccine to induce a mucosal immune response. Meanwhile, the immunization of HBc-N144-NspA without adjuvant induced only mild inflammatory infiltration into the mouse muscle tissue. Conclusion: This study demonstrates that modification using HBc renders NspA a candidate vaccine, which can trigger protective immunity against NMB.


Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vírus da Hepatite B/metabolismo , Infecções Meningocócicas/imunologia , Infecções Meningocócicas/prevenção & controle , Neisseria meningitidis/patogenicidade , Sorogrupo , Vírion/metabolismo , Adjuvantes Imunológicos/farmacologia , Sequência de Aminoácidos , Animais , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/ultraestrutura , Citocinas/metabolismo , Escherichia coli/metabolismo , Feminino , Imunidade , Imunização , Inflamação/patologia , Ativação Linfocitária/imunologia , Infecções Meningocócicas/patologia , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/imunologia , Teste Bactericida do Soro , Baço/microbiologia , Linfócitos T/imunologia , Vacinação , Virulência
9.
Int J Biol Macromol ; 141: 893-905, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31518619

RESUMO

We investigated UV-shielding performances and biodegradation abilities under controlled hydrolytic, soil burial, and thermal conditions of transparent polylactic acids (PLA) nanocomposite films embedded with cellulose nanocrystal-zinc oxide (CNC-ZnO) hybrids. By adding high content of 15wt %CNC-ZnO hybrids into the PLA matrix, the highest UV radiation was blocked out by (85.31%) of UV-A and (95.90%) of UV-B. It is found that the weight loss of PLA nanocomposites after being hydrolytic degraded for 70 days increased from 9% for PLA to 25% with 15 wt% CNC-ZnO hybrids. Meanwhile, in soil burial test, pure PLA shows smallest degradation rate with only 8% weight loss after 110 days, while the PLA nanocomposite film with 15 wt% CNC-ZnO hybrids was degraded by about 28%. Besides, the resultant degradation byproducts from the thermally-decomposed catalysis have been identified by Fourier transform infrared spectroscopy (FT-IR). Moreover, the morphologies and appearances changes during the hydrolytic and soil degradation of PLA nanocomposite films were evaluated. This study is expected to provide meaningful insights into nanocomposite films embedded with CNC-ZnO hybrids as a result of contourable degradation and high ultraviolet protection factor value (UPF).

11.
J Agric Food Chem ; 67(39): 10954-10967, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31365242

RESUMO

High-performance and useful graphene oxide (GO) and cellulose nanocrystals (CNCs) are easily extracted from natural graphite and cellulose raw materials, and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is produced by bacterial fermentation from natural plant corn stalks, etc. In this study, novel ternary nanocomposites consisting of PHBV/cellulose nanocrystal-graphene oxide nanohybrids were prepared via a simple solution casting method. The synergistic effect of CNC with GO nanohybrids obtained by chemical grafting (CNC-GO, covalent bonds) and physical blending (CNC/GO, noncovalent bonds) on the physicochemical properties of PHBV nanocomposites was evaluated and the results compared with a single component nanofiller (CNC or GO) in binary nanocomposites. More interestingly, ternary nanocomposites displayed the highest thermal stability and mechanical properties. Compared to neat PHBV, the tensile strength and elongation to break increased by 170.2 and 52.1%, respectively, and maximum degradation temperature (Tmax) increment by 26.3 °C, were observed for the ternary nanocomposite with 1 wt % covalent bonded CNC-GO. Compared to neat PHBV, binary, and 1:0.5 wt % noncovalent CNC/GO based nanocomposites, the ternary nanocomposites with 1 wt % covalent bonded CNC-GO exhibited excellent barrier properties, good antibacterial activity (antibacterial ratio of 100.0%), reduced barrier properties, and lower migration level for both food simulants. Such a synergistic effect yielded high-performance ternary nanocomposites with great potential for bioactive food packaging materials.


Assuntos
Celulose/química , Embalagem de Alimentos/instrumentação , Grafite/química , Nanocompostos/química , Nanopartículas/química , Poliésteres/química , Celulose Oxidada , Temperatura Ambiente , Resistência à Tração
12.
Bioinformatics ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31373607

RESUMO

MOTIVATION: T and B cell receptors (TCRs and BCRs) play a pivotal role in the adaptive immune system by recognizing an enormous variety of external and internal antigens. Understanding these receptors is critical for exploring the process of immunoreaction and exploiting potential applications in immunotherapy and antibody drug design. Although a large number of samples have had their TCR and BCR repertoires sequenced using high-throughput sequencing in recent years, very few databases have been constructed to store these kinds of data. To resolve this issue, we developed a database. RESULTS: We developed a database, the Pan Immune Repertoire Database (PIRD), located in China National GeneBank (CNGBdb), to collect and store annotated TCR and BCR sequencing data, including from Homo sapiens and other species. In addition to data storage, PIRD also provides functions of data visualisation and interactive online analysis. Additionally, a manually curated database of TCRs and BCRs targeting known antigens (TBAdb) was also deposited in PIRD. AVAILABILITY AND IMPLEMENTATION: PIRD can be freely accessed at https://db.cngb.org/pird.

13.
ACS Appl Mater Interfaces ; 11(27): 24435-24446, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31257847

RESUMO

Nature employs supramolecular self-assembly to organize many molecularly complex structures. Based on this, we now report for the first time the supramolecular self-assembly of 3D lightweight nanocellulose aerogels using carboxylated ginger cellulose nanofibers and polyaniline (PANI) in a green aqueous medium. A possible supramolecular self-assembly of the 3D conductive supramolecular aerogel (SA) was provided, which also possessed mechanical flexibility, shape recovery capabilities, and a porous networked microstructure to support the conductive PANI chains. The lightweight conductive SA with hierarchically porous 3D structures (porosity of 96.90%) exhibited a high conductivity of 0.372 mS/cm and a larger area-normalized capacitance (Cs) of 59.26 mF/cm2, which is 20 times higher than other 3D chemically cross-linked nanocellulose aerogels, fast charge-discharge performance, and excellent capacitance retention. Combining the flexible SA solid electrolyte with low-cost nonwoven polypropylene and PVA/H2SO4 yielded a high normalized capacitance (Cm) of 291.01 F/g without the use of adhesive that was typically required for flexible energy storage devices. Furthermore, the supramolecular conductive aerogel could be used as a universal sensitive sensor for toxic gas, field sobriety tests, and health monitoring devices by utilizing the electrode material in lightweight supercapacitor and wearable flexible devices.

14.
Cancer Med ; 8(9): 4254-4264, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199589

RESUMO

Cancer patients have been treated with various types of therapies, including conventional strategies like chemo-, radio-, and targeted therapy, as well as immunotherapy like checkpoint inhibitors, vaccine and cell therapy etc. Among the therapeutic alternatives, T-cell therapy like CAR-T (Chimeric Antigen Receptor Engineered T cell) and TCR-T (T Cell Receptor Engineered T cell), has emerged as the most promising therapeutics due to its impressive clinical efficacy. However, there are many challenges and obstacles, such as immunosuppressive tumor microenvironment, manufacturing complexity, and poor infiltration of engrafted cells, etc still, need to be overcome for further treatment with different forms of cancer. Recently, the antitumor activities of CAR-T and TCR-T cells have shown great improvement with the utilization of CRISPR/Cas9 gene editing technology. Thus, the genome editing system could be a powerful genetic tool to use for manipulating T cells and enhancing the efficacy of cell immunotherapy. This review focuses on pros and cons of various gene delivery methods, challenges, and safety issues of CRISPR/Cas9 gene editing application in T-cell-based immunotherapy.

15.
Genes (Basel) ; 10(6)2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167502

RESUMO

One of the most commonly encountered species in the small basidiomycetous sub-phylum Wallemiomycotina is Wallemia mellicola, a xerotolerant fungus with a widespread distribution. To investigate the population characteristics of the species, whole genomes of twenty-five strains were sequenced. Apart from identification of four strains of clonal origin, the distances between the genomes failed to reflect either the isolation habitat of the strains or their geographical origin. Strains from different parts of the world appeared to represent a relatively homogenous and widespread population. The lack of concordance between individual gene phylogenies and the decay of linkage disequilibrium indicated that W. mellicola is at least occasionally recombining. Two versions of a putative mating-type locus have been found in all sequenced genomes, each present in approximately half of the strains. W. mellicola thus appears to be capable of (sexual) recombination and shows no signs of allopatric speciation or specialization to specific habitats.

16.
J Exp Clin Cancer Res ; 38(1): 261, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200735

RESUMO

BACKGROUND & AIMS: Although the prognosis of patients with occult hepatitis B virus (HBV) infection (OBI) is usually benign, a small portion may undergo cirrhosis and subsequently hepatocellular carcinoma (HCC). We studied the mechanism of life-long Integration of virus DNA into OBI host's genome, of which may induce hepatocyte transformation. METHODS: We applied HBV capture sequencing on single cells from an OBI patient who, developed multiple HCC tumors and underwent liver resection in May 2013 at Tongji Hospital in China. Despite with the undetectable virus DNA in serum, we determined the pattern of viral integration in tumor cells and adjacent non-tumor cells and obtained the details of the viral arrangement in host genome, and furthermore the HBV integrated region in cancer genome. RESULTS: HBV captured sequencing of tissues and individual cells revealed that samples from multiple tumors shared two viral integration sites that could affect three host genes, including CSMD2 on chr1 and MED30/EXT1 on chr8. Whole genome sequencing further indicated one hybrid chromosome formed by HBV integrations between chr1 and chr8 that was shared by multiple tumors. Additional 50 poorly differentiated liver tumors and the paired adjacent non-tumors were evaluated and functional studies suggested up-regulated EXT1 expression promoted HCC growth. We further observed that the most somatic mutations within the tumor cell genome were common among the multiple tumors, suggesting that HBV associated, multifocal HCC is monoclonal in origin. CONCLUSION: Through analyzing the HBV integration sites in multifocal HCC, our data suggested that the tumor cells were monoclonal in origin and formed in the absence of active viral replication, whereas the affected host genes may subsequently contribute to carcinogenesis.

17.
Medicine (Baltimore) ; 98(22): e15749, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145289

RESUMO

RATIONALE: Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults. The first choice for GBM is surgery, and followed by a combination of radiotherapy and chemotherapy. There are limited treatments for patients with recurrent GBM. Relapsed patients usually have a worse prognosis, and with a median survival time of <6 months. Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor that can inhibit tumor angiogenesis and inhibit tumor cell growth. This drug has been used to treat advanced lung cancer. PATIENT CONCERNS: We present a case of recurrent GBM was treated with anlotinib in this report. The patient was diagnosed with GBM in August 2016 and treated with surgery and temozolomide (TMZ) chemotherapy. She was diagnosed with recurrence in February 2017 following which she was treated with gamma knife and TMZ chemotherapy. In November 2017, the patient presented with decreased vision in left eye. She was given radiation and her left eye vision returned to normal after radiation. On May23, 2018, the patient reported a decrease in left visual acuity again. DIAGNOSES: Brain magnetic resonance imaging (MRI) showed progression of the disease, and the tumor invaded the left optic nerve. INTERVENTIONS: This patient was administer anlotinib 12 mg po qd (d1-14, 21days as a cycle). Three cycles anlotinib were given to this patient. OUTCOMES: The patient reported her left visual acuity increased over 10 days after first cycle of anlotinib treatment. MRI scan revealed tumor volume shrinks, especially the part that invades the left optic nerve shrinks significantly at 26 days after anlotinib treatment on August 11, 2018. However, the tumor progressed in 2 months after using of anlotinib. From the beginning of the application of anlotinib to death, her survival time was 110 days. LESSONS: Anlotinib treatment with mild side effects may be a new option for the patients with recurrent glioblastoma.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Indóis/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Quinolinas/uso terapêutico , Neoplasias Encefálicas/patologia , Evolução Fatal , Feminino , Glioblastoma/patologia , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/patologia
18.
Gigascience ; 8(5)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31049560

RESUMO

BACKGROUND: For both pediatric and adult patients, umbilical cord blood (UCB) transplant is a therapeutic option for a variety of hematologic diseases, such as blood cancers, myeloproliferative disorders, genetic diseases, and metabolic disorders. However, the level of cellular heterogeneity and diversity of nucleated cells in UCB has not yet been assessed in an unbiased and systemic fashion. In the present study, nucleated cells from UCB were subjected to single-cell RNA sequencing to simultaneously profile the gene expression signatures of thousands of cells, generating a rich resource for further functional studies. Here, we report the transcriptomes of 17,637 UCB cells, covering 12 major cell types, many of which can be further divided into distinct subpopulations. RESULTS: Pseudotemporal ordering of nucleated red blood cells identifies wave-like activation and suppression of transcription regulators, leading to a polarized cellular state, which may reflect nucleated red blood cell maturation. Progenitor cells in UCB also comprise 2 subpopulations with activation of divergent transcription programs, leading to specific cell fate commitment. Detailed profiling of cytotoxic cell populations unveiled granzymes B and K signatures in natural killer and natural killer T-cell types in UCB. CONCLUSIONS: Taken together, our data form a comprehensive single-cell transcriptomic landscape that reveals previously unrecognized cell types, pathways, and mechanisms of gene expression regulation. These data may contribute to the efficacy and outcome of UCB transplant, broadening the scope of research and clinical innovations.

19.
J Pain ; 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31085334

RESUMO

Our preliminary experiment indicated the activation of with-nolysine kinases 1 (WNK1) in bone cancer pain (BCP) rats. This study aimed to investigate the underlying mechanisms via which WNK1 contributed to BCP. A rat model of BCP was induced by Walker-256 tumor cell implantation. WNK1 expression and distribution in the lumbar spinal cord dorsal horn and dorsal root ganglion were examined. SPS1-related proline/alanine-rich kinase (SPAK), oxidative stress-responsive kinase 1 (OSR1), sodium-potassium-chloride cotransporter 1 (NKCC1), and potassium-chloride cotransporter 2 (KCC2) expression were assessed. Pain behaviors including mechanical allodynia and movement-evoked pain were measured. BCP rats exhibited significant mechanical allodynia, with increased WNK1 expression in the dorsal horn and dorsal root ganglion neurons, elevated SPAK/OSR1 and NKCC1 expression in the dorsal root ganglion, and decreased KCC2 expression in the dorsal horn. WNK1 knock-down by small interfering alleviated mechanical allodynia and movement-evoked pain, inhibited WNK1-SPAK/OSR1-NKCC1 activities, and restored KCC2 expression. In addition, closantel (a WNK1-SPAK/OSR1 inhibitor) improved pain behaviors, downregulated SPAK/OSR1 and NKCC1 expression, and upregulated KCC2 expression in BCP rats. Activation of WNK1-SPAK/OSR1 signaling contributed to BCP in rats by modulating NKCC1 and KCC2 expression. Therefore, suppression of WNK1-SPAK/OSR1 may serve as a potential target for BCP therapy. PERSPECTIVE: Our findings demonstrated that the WNK1-SPAK/OSR1 signaling contributed to BCP in rats via regulating NKCC1 and KCC2. Suppressing this pathway reduced pain behaviors. Based on these findings, the WNK1-SPAK/OSR1 signaling may be a potential target for BCP therapy.

20.
Int J Mol Sci ; 20(7)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987273

RESUMO

Chitin deacetylases (CDAs) are a group of enzymes involved in chitin metabolism in insects; they play a critical role in molting, pupation, and the modification of chitin. In this study, we identified several CDAs in the silkworm, Bombyx mori (BmCDA), and investigated the effect of various hormones on their expression in B. mori larvae and embryo cell lines (BmE). Eight genes encoding BmCDAs were identified in the silkworm genome. They showed different expression patterns in different tissues, and were classified into three types based on where they were expressed: the exoskeleton, digestive organs, and genital organs. Moreover, we found that some BmCDAs showed upregulated expression during the molting period, especially during the fourth molting period in larvae. We also verified that the expression of BmCDA1-6 was upregulated by treatment with 20-hydroxyecdysone not only in larvae, but also in BmE cells. Interestingly, juvenile hormone analog treatment also upregulated the expression of some BmCDAs. The overexpression of several transcription factors revealed that the POU transcription factor POUM2 may play a major role in the regulation of BmCDA expression. Finally, the silencing of BmCDA1 and BmCDA2 did not lead to abnormal phenotypes or death, but may have led to delays in silkworm pupation. These results provide important information about lepidopteran insects in terms of chitin deacetylases and the regulation of their expression.


Assuntos
Amidoidrolases/metabolismo , Bombyx/enzimologia , Bombyx/metabolismo , Estudo de Associação Genômica Ampla/métodos , Animais , Ecdisterona/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Insetos/metabolismo , Hormônios Juvenis/metabolismo , Muda/fisiologia
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