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1.
J Nanosci Nanotechnol ; 20(2): 673-679, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383062

RESUMO

A proper soft tissue seal between implants and gingiva is critical for success of dental implants. Implant surface modification is an important approach for achieving ideal host-implant integration. In this study, we used a new and simple oxidation method to generate a rough surface on implants at the nano scale, which oxidized titanium nano-foveolae (TiNF) surface. We further analyzed the surface topography and tested its effects on biological activities of human gingival fibroblasts. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) examination demonstrated that TiNF disks displayed uniform rough surfaces, with average TiNF diameters of approximately 60 nm and 100 nm respectively. However, the surfaces of smooth samples were highly irregular, and cell adhesion and proliferation rates on TiNF surfaces were significantly higher than those of the smooth surfaces. Extracellular matrix synthesis was also increased in the cells that interacted with oxidized TiNF surfaces. Altogether, these results suggest that the TiNF implant surfaces perform better for human gingival fibroblast biological activities compared to traditional smooth surfaces. Therefore, the TiNF implant surfaces may serve as ideal interface to facilitate implant-host integration.

2.
Nanotechnology ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31469106

RESUMO

In this study, we employed microwave plasma assisted reduction (MPAR) method for preparing metallic nanoparticles with desirable morphology. Compared with hydrogen thermal reduction technique, MPAR technique could greatly maintain the original morphology of self-sacrificing precursors, as well as is proved to be high-efficiency, energy-saving and pollution-free. Taking ferromagnetic metallic Co as forerunner, Co nanosheets with inerratic hexagonal morphology were successfully synthesized on a large scale uniformly. The lateral dimension of achieved Co nanosheets is in the range of 3~5 µm with tens of nanometers in thickness. The intact hexagonal flaky shape of Co nanosheets is beneficial for improving dielectric loss by increasing electric channels and interfacial polarization. Consequently, the minimum reflection loss could reach up to -71 dB at a thin thickness of 1.2 mm. Furthermore, the effective bandwidth (RL﹤-10 dB) could be achieved in a wide range of 2.8~18 GHz by integrating the thickness from 5.0~1.0 mm, which provide the possible for applications in electromagnetic shielding and radar stealth fields. It is believed that MPAR technique is suitable for designing and preparing novel microwave absorbers on the basis of appropriate precursors, providing new opportunities for acquiring high performance microwave absorbers in the future.

3.
J Med Food ; 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31259654

RESUMO

Naringin and its aglycone, naringenin, occur naturally in our regular diet and traditional Chinese medicines. This study aimed to detect an effective therapeutic approach for cough variant asthma (CVA) through evaluating the relaxant effect of these two bioactive herbal monomers as antitussive and antiasthmatic on rat tracheal smooth muscle. The relaxant effect was determined by measuring muscular tension with a mechanical recording system in rat tracheal rings. Cytosolic Ca2+ concentration was measured using a confocal imaging system in primary cultured tracheal smooth muscle cells. In rat tracheal rings, addition of both naringin and naringenin could concentration dependently relax carbachol (CCh)-evoked tonic contraction. This epithelium-independent relaxation could be suppressed by BaCl2, tetraethylammonium, and iberiotoxin (IbTX), but not by glibenclamide. After stimulating primary cultured tracheal smooth muscle cells by CCh or high KCl, the intracellular Ca2+ increase could be inhibited by both naringin and naringenin, respectively. This reaction was also suppressed by IbTX. These results demonstrate that both naringin and naringenin can relax tracheal smooth muscle through opening big conductance Ca2+-activated K+ channel, which mediates plasma membrane hyperpolarization and reduces Ca2+ influx. Our data indicate a potentially effective therapeutic approach of naringin and naringenin for CVA.

4.
J Agric Food Chem ; 67(30): 8348-8360, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31304751

RESUMO

We have recently demonstrated that tau hyperphosphorylation causes diabetic synaptic neurodegeneration of retinal ganglion cells (RGCs), which might be the earliest affair during the pathogenesis of diabetic retinopathy (DR). Thus, there is a pressing need to seek therapeutic agents possessing neuroprotective effects against tau hyperphosphorylation in RGCs for arresting the progression of DR. Here, using a well-characterized diabetes model of db/db mouse, we discovered that topical ocular application of 10 mg/kg/day of ginsenoside Rg1 (GRg1), one of the major active ingredients extracted from Panax ginseng and Panax notoginseng, ameliorated hyperphosphorylated tau-triggered RGCs synaptic neurodegeneration in diabetic mice. The neuroprotective effects of GRg1 on diabetic retinae were abrogated when retinal IRS-1 or Akt was suppressed by intravitreal injection with si-IRS-1 or topically coadministered with a specific inhibitor of Akt, respectively. However, selective repression of retinal GSK3ß by intravitreal administration of si-GSK3ß rescued the neuroprotective properties of GRg1 when Akt was inactivated. Therefore, the present study showed for the first time that GRg1 can prevent hyperphosphorylated tau-induced synaptic neurodegeneration of RGCs via activation of IRS-1/Akt/GSK3ß signaling in the early phase of DR. Moreover, our data clarify the potential therapeutic significance of GRg1 for neuroprotective intervention strategies of DR.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Ginsenosídeos/administração & dosagem , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Ganglionares da Retina/efeitos dos fármacos , Proteínas tau/metabolismo , Animais , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Neural/tratamento farmacológico , Degeneração Neural/genética , Degeneração Neural/metabolismo , Panax notoginseng/química , Fosforilação , Extratos Vegetais/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/genética , Retina/patologia , Células Ganglionares da Retina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas tau/genética
5.
Biol Trace Elem Res ; 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286389

RESUMO

Cadmium (Cd) is the most common heavy metal and is easily detected in aquatic environments on a global scale. Vitamin C was a widely used vitamin in aquaculture. The aim of this study was to explore the potential of vitamin C in ameliorating Cd-induced toxicity in grass carp kidney (CIK) cells. Cell viability, oxidative response, metallothionein (MT), and immune-related gene expression was analyzed in the present study. The results show that cell viability was significantly reduced following Cd exposure, but the vitamin C supplementation attenuated the increased in cell viability. In addition, vitamin C supplementation can increase the antioxidation response and MT and immune-related gene expression. These results indicate that vitamin C has the potential to alleviate the effects of Cd toxicity in CIK cells.

6.
Int J Mol Sci ; 20(14)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31336784

RESUMO

The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified N-methylparoxetine (NMP) as an inducer of mitochondrial fragmentation with subsequent apoptosis in non-small cell lung cancer (NSCLC) cells. We discovered that ROS was accumulated in NMP-treated NSCLC cells, followed by c-Jun N-terminal kinase (JNK) and p38 MAP kinase (p38) activation. This was reversed by the application of a reactive oxygen species (ROS) scavenger, N-acetylcysteine (NAC), leading to a reduction in apoptosis. Our data suggested that NMP induced apoptosis in NSCLC cells by activating mitogen-activated protein kinase (MAPK) pathway. We further speculated that the remarkable increase of ROS in NMP-treated NSCLC cells might result from an inhibition of autophagy. Our current data confirmed that NMP blocked autophagy flux at late stage wherein lysosomal acidification was inhibited. Taken together, this study demonstrated that NMP could exert dual apoptotic functions-mitochondria impairment and, concomitantly, autophagy inhibition. NMP-related excessive ROS accumulation induced apoptosis by activating the MAPK pathway in NSCLC cells.

7.
Nanoscale ; 11(30): 14123-14133, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31322633

RESUMO

Quantum dots, derived from two-dimensional (2D) materials, have shown promise in bioimaging, sensing and photothermal applications, and in white light emitting devices (WLEDs). Herein, nitrogen and phosphorus functionalized Ti3C2 MXene based quantum dots (N,P-MQDs) were successfully prepared through a top-bottom hydrothermal method. This type of photoluminescent quantum dots has realized green fluorescence for the first time at around 560 nm with a photoluminescence quantum yield (PLQY) of 20.1%, the highest ever reported; meanwhile, it also exhibits excellent photostability and pH resistance capacities. Comprehensive characterization and well-resolved density functional theory (DFT) calculation were implemented to determine the mechanism of fluorescence shift and enhancement. Furthermore, the N,P-MQDs have been proved to efficiently act as fluorescent probes for macrophage labeling. In addition, the high sensitivity of the N,P-MQDs toward Cu2+ ions made them a low cost, sensitive, environment-friendly, and label-free fluorescence platform for Cu2+ detection. The outstanding performance of Ti3C2 MXene based quantum dots has demonstrated their great potential to be used as promising fluorescent probes in the fields of biological imaging, optical sensing, photoelectric conversion, etc.

8.
Int J Parasitol ; 49(9): 697-704, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31254529

RESUMO

Trichomonas vaginalis is a primary urogenital parasite that causes trichomoniasis, a common sexually transmitted disease. As the first line of host defense, vaginal epithelial cells play critical roles in orchestrating vaginal innate immunity and modulate intracellular Cl- homeostasis via the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel that plays positive roles in regulating nuclear factor-κB (NF-κB) signalling. However, the association between T. vaginalis infection and intracellular Cl- disequilibrium remains elusive. This study showed that after T. vaginalis infection, CFTR was markedly down-regulated by cysteine proteases in vaginal epithelial cells. The intracellular Cl- concentration ([Cl-]i) was consequently elevated, leading to NF-κB signalling activation via serum- and glucocorticoid-inducible kinase-1. Moreover, heightened [Cl-]i and activated NF-κB signalling could be sustained in a positive feedback regulatory manner resulting from decreased intracellular cAMP through NF-κB-mediated up-regulation of phosphodiesterase 4. The results conclusively revealed that the intracellular Cl- of the human vaginal epithelium could be dynamically modulated by T. vaginalis, which contributed to mediation of epithelial inflammation in the human vagina.

9.
Nitric Oxide ; 90: 37-46, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31175932

RESUMO

Endometrial epithelium exhibits a robust ion transport activity required for dynamical regulation of uterine fluid environment and thus embryo implantation. However, there still lacks a thorough understanding of the ion transport processes and regulatory mechanism in peri-implantation endometrial epithelium. As a gaseous signaling molecule or gasotransmitter, hydrogen sulfide (H2S) regulates a myriad of cellular and physiological processes in various tissues, including the modulation of ion transport proteins in epithelium. This study aimed to investigate the effects of H2S on ion transport across mouse endometrial epithelium and its possible role in embryo implantation. The existence of endogenous H2S in pregnant mouse uterus was tested by the detection of two key H2S-generating enzymes and measurement of H2S production rate in tissue homogenates. Transepithelial ion transport processes were electrophysiologically assessed in Ussing chambers on early pregnant mouse endometrial epithelial layers, demonstrating that H2S suppressed the anion secretion by blocking cystic fibrosis transmembrane conductance regulator (CFTR). H2S increased intracellular Cl- concentration ([Cl-]i) in mouse endometrial epithelial cells, which was abolished by pretreatment with the CFTR selective inhibitor CFTRinh-172. The cAMP level in mouse endometrial epithelial cells was not affected by H2S, indicating that H2S blocked CFTR in a cAMP-independent way. In vivo study showed that interference with H2S synthesis impaired embryo implantation. In conclusion, our study demonstrated that H2S inhibits the transepithelial anion secretion of early pregnant mouse endometrial epithelium via blockade of CFTR, contributing to the preparation for embryo implantation.

10.
Biosens Bioelectron ; 138: 111302, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31112917

RESUMO

The early detection of bacterium plays a significant role in addressing serious public health issues. In this paper, a supersensitive multichannel series piezoelectric quartz crystal (MSPQC) sensor of bacterium based on 16S rRNA and "DNA-RNA switch" was constructed. The fragment in specific region of 16S rRNA was used as the biomarker of bacterium to ensure high specificity and to achieve the accurate judgment of microbial vitality. "DNA-RNA switch" was designed to conduct two electrodes by switching insulated "gene-link" into conductive "silver-link", which achieved the super-sensitivity of MSPQC to bacteria. To demonstrate the feasibility of this strategy, a proof-of-concept method for Escherichia coli (E. coli) assay was designed. The detection limit was down to 2 cfu/mL. Staphylococcus aureus, Salmonella enteritidis, Listeria innocua and Pseudomonas aeruginosa did not interfere with the detection results. Proposed method was highly sensitive, and specific for bacterium detection, which might find widely use in early detection of bacterium in the field of public safety monitoring and clinical diagnosis.

11.
ACS Nano ; 13(5): 5291-5305, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31074967

RESUMO

Nanoenabled foliar-applied agrochemicals can potentially be safer and more efficient than conventional products. However, limited understanding about how nanoparticle properties influence their interactions with plant leaves, uptake, translocation through the mesophyll to the vasculature, and transport to the rest of the plant prevents rational design. This study used a combination of Au quantification and spatial analysis to investigate how size (3, 10, or 50 nm) and coating chemistry (PVP versus citrate) of gold nanoparticles (AuNPs) influence these processes. Following wheat foliar exposure to AuNPs suspensions (∼280 ng per plant), adhesion on the leaf surface was increased for smaller sizes, and PVP-AuNPs compared to citrate-AuNPs. After 2 weeks, there was incomplete uptake of citrate-AuNPs with some AuNPs remaining on the outside of the cuticle layer. However, the fraction of citrate-AuNPs that had entered the leaf was translocated efficiently to the plant vasculature. In contrast, for similar sizes, virtually all of the PVP-AuNPs crossed the cuticle layer after 2 weeks, but its transport through the mesophyll cells was lower. As a consequence of PVP-AuNP accumulation in the leaf mesophyll, wheat photosynthesis was impaired. Regardless of their coating and sizes, the majority of the transported AuNPs accumulated in younger shoots (10-30%) and in roots (10-25%), and 5-15% of the NPs <50 nm were exuded into the rhizosphere soil. A greater fraction of larger sizes AuNPs (presenting lower ζ potentials) was transported to the roots. The key hypotheses about the NPs physical-chemical and plant physiology parameters that may matter to predict leaf-to-rhizosphere transport are also discussed.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30999648

RESUMO

Since few studies evaluated the impact of the global budget payment system (GBPS) over time, and by expenditure type, this paper aims to evaluate the impact of the GBPS on expenditure of inpatients, and explores how hospitals curb the expenditure in patients with cardiovascular diseases (CVDs) in Shanghai. We built a time series model with the monthly expenditure of CVDs from 2009 to 2012. We evaluated the instant impact and trends impact of the GBPS and analyzed results based on medical expenditure types (e.g., drug, examination, cure, unclassified items), discharge number, and expenditure per capita. We found GBPS instantly dropped the medical expenditure by Chinese Yuan (CNY) 55.71 million (p < 0.001), and decreased the monthly increasing trend by CNY 4.23 million (p = 0.011). The discharge number had 10.4% instant reduction and 225.55 monthly decrease (p = 0.021) while the expenditure per capita experienced fewer changes. Moreover, the expenditure of drug and cure had an instant reduction of CNY 28.31 million and 16.28 million (p < 0.001). In conclusion, we considered the GBPS is an effective solution to control the expenditure of CVDs by decreasing the discharge number, and a focus on the drug and cure expenditures lead to greater spend reduction than other types of expenditures.

13.
Neuropharmacology ; 153: 1-12, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31015047

RESUMO

Diabetic retinal neurodegeneration, in particular synaptic neurodegeneration of retinal ganglion cells (RGCs) occurring before RGCs apoptosis, may represent the earliest event in the pathogenesis of diabetic retinopathy (DR). Our previous study identified hyperphosphorylated-tau as a critical toxic mediator in diabetic RGCs synaptic neurodegeneration. Thus, therapeutic agents targeting to tau may appear as a promising strategy to arrest the progression of DR. The glucagon-like-peptide 1 receptor (GLP-1R) agonists, including liraglutide, can ameliorate neurodegenerative features in models of Alzheimer's disease and diabetes by decreasing tau hyperphosphorylation in the brain. Liraglutide has also been found to prevent retinal neural apoptosis/loss in diabetic mice. However, whether liraglutide can prevent diabetic synapse degeneration of RGCs, and its neuroprotective role, if any, is due to alleviating retinal tau hyperphosphorylation remain unknown. Here, using a well characterized high-fat diet (HFD)-induced diabetes mouse model, we showed that topical ocular administration of liraglutide reversed hyperphosphorylated tau-triggered RGCs synaptic degeneration in HFD-induced diabetes. The neuroprotective effect of liraglutide on diabetic retinae was abolished when GLP-1R or Akt was inhibited by topically co-administration with a GLP-1R antagonist, exendin-(9-39), or an Akt inhibitor MK2206, respectively. However, knock-down of GSK3ß by intravitreal injection of si-GSK3ß restored the neuroprotective effects of liraglutide abrogated by Akt inactivation. Thus, our present study demonstrated that liraglutide can arrest hyperphosphorylated tau-triggered retinal neurodegeneration via activation of GLP-1R/Akt/GSK3ß signaling. Our results also propose that topical ocular application of liraglutide can be envisaged as a potentially useful strategy for the treatment of retinal tauopathy at the early onset of DR.

14.
Langmuir ; 35(19): 6379-6386, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30990696

RESUMO

Geckos have adapted to the complicated natural environment with its excellent climbing ability. Current artificial gecko-inspired synthetic adhesives (GSAs) mimic gecko's attach-detach mechanism by creating anisotropic and hierarchical structures. Easy detachment and high self-cleaning capability are still the unsolved problems in GSAs. This study presents an unprecedented photodetachable mechanism of making bioinspired smart surfaces utilizing carbon dot (CD)-doped polydimethylsiloxane (PDMS) composites. Under ultraviolet (UV) irradiation, it could be triggered up to 80.46% reduction of adhesion force between PDMS-CDs bioinspired surfaces and contaminating particles. A load-drag-pull (i.e., LDP) test mimicking gecko's locomotion was adopted to test the dry self-cleaning capabilities of these bioinspired surfaces, where the falling rate of the model contaminates (PS micropellets; average size in diameter ∼8 µm) can reach up to 54.83% after seven repeated steps under UV irradiation. The significantly improved dry self-cleaning capability is attributed to the photothermal effect of CDs inside the PDMS matrix. The mechanism proposed in this work will find its applications in the realms of climbing robots, space adhesive devices, and self-cleaning, advanced gripping technologies for pick and place or assembly.

15.
Molecules ; 24(6)2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30934584

RESUMO

Metallo-ß-lactamases (MßLs) are the target enzymes of ß-lactam antibiotic resistance, and there are no effective inhibitors against MßLs available for clinic so far. In this study, thirteen halogen-substituted triazolethioacetamides were designed and synthesized as a potent skeleton of MßLs inhibitors. All the compounds displayed inhibitory activity against ImiS with an IC50 value range of 0.032⁻15.64 µM except 7. The chlorine substituted compounds (1, 2 and 3) inhibited NDM-1 with an IC50 value of less than 0.96 µM, and the fluorine substituted 12 and 13 inhibited VIM-2 with IC50 values of 38.9 and 2.8 µM, respectively. However, none of the triazolethioacetamides exhibited activity against L1 at inhibitor concentrations of up to 1 mM. Enzyme inhibition kinetics revealed that 9 and 13 are mixed inhibitors for ImiS with Ki values of 0.074 and 0.27µM using imipenem as the substrate. Docking studies showed that 1 and 9, which have the highest inhibitory activity against ImiS, fit the binding site of CphA as a replacement of ImiS via stable interactions between the triazole group bridging ASP120 and hydroxyl group bridging ASN233.


Assuntos
Halogênios/química , Tioacetamida/química , Tioacetamida/farmacologia , Inibidores de beta-Lactamases/química , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/química , Sítios de Ligação , Relação Dose-Resposta a Droga , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade , Tioacetamida/análogos & derivados
16.
Langmuir ; 35(13): 4527-4533, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30845803

RESUMO

According to the fact that gecko-inspired vertically aligned carbon nanotubes (VA-CNTs) exhibit ultrastrong adhesion, dopamine is utilized to make a modification to this traditional biomimetic material. The composite material is tested for adhesion performance under different environmental conditions by an atomic force microscope. The adhesion force of the modified VA-CNTs does not show obvious fluctuation during the gradual heating process; however, the material gains improved adhesion when increasing the ambient humidity. In addition, the modified CNTs show a stronger adhesion force than the original CNTs in their performance tests. The dopamine polymer has a good combination with CNTs, which is responsible for the aforementioned excellent performance. Overall, this modification method is simple, convenient, efficient, and environmentally friendly, which all indicates a promising future in its application. The modified CNTs are expected to be used for super-adhesion in harsh environments, as well as in the field of microelectronics.

17.
Environ Sci Technol ; 53(9): 4959-4967, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30920811

RESUMO

The objectives of this research were to quantify the impact of organic matter content, soil pH and moisture content on the dissolution rate and solubility of copper oxide nanoparticles (CuO NPs) in soil, and to develop an empirical model to predict the dissolution kinetics of CuO NPs in soil. CuO NPs were dosed into standard LUFA soils with various moisture content, pH and organic carbon content. Chemical extractions were applied to measure the CuO NP dissolution kinetics. Doubling the reactive organic carbon content in LUFA 2.1 soil increased the solubility of CuO NP 2.7-fold but did not change the dissolution rate constant. Increasing the soil pH from 5.9 to 6.8 in LUFA 2.2 soil decreased the dissolution rate constant from 0.56 mol1/3·kg1/3·s-1 to 0.17 mol1/3·kg1/3·s-1 without changing the solubility of CuO NP in soil. For six soils, the solubility of CuO NP correlated well with soil organic matter content ( R2 = 0.89) independent of soil pH. In contrast, the dissolution rate constant correlated with pH for pH < 6.3 ( R2 = 0.89), independent of soil organic matter content. These relationships predicted the solubility and dissolution rate constants of CuO NP in two test soils (pH 5.0 and pH 7.6). Moisture content showed negligible impact on the dissolution kinetics of CuO NPs. Our study suggests that soil pH and organic matter content affect the dissolution behavior of CuO NP in soil in a predictable manner.

18.
Fish Shellfish Immunol ; 88: 161-169, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30802628

RESUMO

Lysozyme is an important defense molecule of the innate immune system and possess high antimicrobial activities. In this study, a full-length c-type lysozyme cDNA (Fplysc) was cloned and characterized from Fenneropenaeus penicillatus. The cDNA contains an open reading frame of 477 bp encoding 158 amino acids, with 53-94% identity with those of other crustaceans. The recombinant Fplysc had antibacterial activities against Gram-positive bacteria (Streptococcus agalactiae and Micrococcus luteus) and Gram-negative bacteria (Vibrio alginolyticus and Escherichia coli), and showed antiviral activity against WSSV and IHHNV. The qRT-PCR analysis showed that Fplysc expression levels were most abundant in hemocytes and less in eyestalk. The expression levels of Fplysc were significantly upregulated in gill, intestine and hemocytes when challenged with WSSV and V. alginolyticus. Fplysc-silencling suppressed Fplysc expression in cephalothoraxes and increased mortality caused by WSSV and V. alginolyticus, and exogenous rFplysc led to a significant decrease of shrimp mortality by injecting rFplysc into Fplysc silenced shrimp, suggesting Fplysc is the important molecule in shrimp antimicrobial and antiviral response. In conclusion, the results provide some insights into the function of Fplysc in shrimp against bacterial and viral infection.


Assuntos
Proteínas de Artrópodes/imunologia , Penaeidae/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Clonagem Molecular , Densovirinae/fisiologia , Escherichia coli/fisiologia , Hemócitos , Imunidade Inata , Micrococcus luteus/fisiologia , Muramidase/química , Muramidase/genética , Muramidase/metabolismo , Penaeidae/genética , Penaeidae/microbiologia , Penaeidae/virologia , Streptococcus agalactiae/fisiologia , Vibrio alginolyticus/fisiologia , Vírus da Síndrome da Mancha Branca 1/fisiologia
19.
J Cell Physiol ; 2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30697740

RESUMO

The vagina provides a characteristic low-Na+ and low-pH fluid microenvironment that is considered generally protective. Previous studies have shown that various types of epithelial cells harbor the capacity of intracellular pH (pHi) regulation. However, it remains elusive whether vaginal epithelium could actively regulate pHi by transporting acid-base ions. In this study, we verified that after transient exposure to NH4 Cl, the pHi values could rapidly recover from acidification via Na+ -H+ exchanger (NHE), Na+ -HCO3 - cotransporter (NBC), and carbonic anhydrase in human vaginal epithelial cell line VK2/E6E7. Positive expression of the main acid-base transporters including NHE1-2, NBCe1-2, and NBCn1 mRNA was also detected in VK2/E6E7 cells. Moreover, the in vivo study further showed that interfering with the function of V-type H+ -ATPase, NHE or NBC expressed in vagina impaired vaginal luminal pH homeostasis in rats. Taken together, our study reveals the property of pH regulation in vaginal epithelial cells, which might provide novel insights into the potential role of vaginal epithelium in the formation of the vaginal acidic microenvironment.

20.
J Hematol Oncol ; 11(1): 141, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572922

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). METHODS: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. RESULTS: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. CONCLUSIONS: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.

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