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1.
Colloids Surf B Biointerfaces ; 241: 113996, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38850745

RESUMEN

Chemo-immunotherapy, which involves the simultaneous use of chemotherapy drug and immunotherapeutic agent to achieve synergistic effects, plays a crucial role in cancer treatment. However, the immunosuppressive microenvironment, insufficient tumor specificity, and serious systemic side effects hinder their synergistic therapeutic effects and clinical applications. Herein, T cell and natural killer (NK) cell, which are the most important immune effector cells, were both activated to reverse the immunosuppressive microenvironment. To simplify drug carriers, oxaliplatin was selected as the chemotherapy drug which can both induce the ICD effect and activate T cells. IL-15 was selected to activate NK cells. To enhance the productivity of the carrier and reduce side effects, the easy-prepared thermosensitive hydrogel (OXL/IL-15 TG) was developed to co-load oxaliplatin-loaded liposomes (OXL) and IL-15. Colorectal cancer, suitable for in situ administration, was selected as model cancer. The resulting novel triple-interlocked combination therapy could directly kill the tumor cells, induces ICD effect and activate NK cells. After administration, OXL/IL-15 TG was formed serving as a drug depot, slowing releasing OXL and IL-15 non-interferencely. OXL around 165.47±7.04 nm was passively delivered to tumor tissue, killing tumor cells and inducing ICD effect. The results demonstrated that IL-15 stimulated the activation of NK cells. In tumor-bearing mice models, OXL/IL-15 TG exhibited a remarkable and noteworthy anti-tumor efficacy, and expanded survival rate. Notably, OXL/IL-15 TG led to an enhanced infiltration of CD3+CD8+ T cells and CD3-CD49+ NK cells within the tumor tissue. Overall, the triple-interlocked combination therapy provided a new idea for colorectal cancer therapy.

2.
BMC Psychol ; 12(1): 360, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902805

RESUMEN

This research delves into the nuances, origins, and societal effects of irrational religious orientations within China's Generation Z, employing grounded theory methodology for a comprehensive analysis. The focus is on those born between 1995 and 2010, a demographic raised amidst rapid information technology growth and significantly influenced by digitalization and globalization. The study identifies three primary dimensions of irrational religious orientations in Generation Z: religious spiritual dependence, religious instrumental tendency, and religious uniqueness identity. These are shaped by factors such as the overwhelming influx of information via digital media, societal pressures and psychological dilemmas, conflicts in values and identity crises, as well as feelings of social isolation and the need for group belonging. To address these trends, the study suggests several interventions: enhancing multicultural and values education, implementing stricter online information regulation and literacy programs, boosting mental health awareness and support, and fostering engagement in social and cultural activities. These recommendations are essential for comprehensively understanding and effectively responding to the irrational religious orientations of Generation Z, ultimately contributing to their overall well-being and healthy development.


Asunto(s)
Teoría Fundamentada , Religión y Psicología , Humanos , Femenino , Masculino , China , Adulto , Persona de Mediana Edad , Identificación Social , Espiritualidad
3.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2689-2698, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38812169

RESUMEN

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.


Asunto(s)
Neoplasias de la Mama , Proliferación Celular , Emulsiones , Verde de Indocianina , Humanos , Verde de Indocianina/química , Células MCF-7 , Emulsiones/química , Proliferación Celular/efectos de los fármacos , Femenino , Tamaño de la Partícula , Geles/química , Nanopartículas/química , Composición de Medicamentos/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Portadores de Fármacos/química
4.
Int J Biol Macromol ; 261(Pt 2): 129840, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38302014

RESUMEN

Double-stranded RNA (dsRNA) can specifically inhibit gene expression by RNA interference and has important application potential in animal disease control. White spot syndrome virus (WSSV) is one of the most harmful pathogens in shrimp aquaculture, causing huge economic losses every year. In this study, we investigated the function of the WSSV-encoded wsv108 protein. We demonstrated that wsv108 could promote apoptosis by interacting with heat shock protein 70 (HSP70) and enhancing the expression of multiple apoptosis-related genes. Silencing of wsv108 gene by injection with specific dsRNA prepared by in vitro transcription significantly increased the survival rate of WSSV-infected shrimp and reduced the viral load in tissues, suggesting that wsv108 is important for WSSV pathogenicity. Based on this, we expressed the wsv108 specific dsRNA in engineered Escherichia coli. Oral feeding of this bacterium could inhibit the expression of wsv108, increase the survival rate of WSSV-infected shrimp, and decrease the viral load of WSSV in tissues. Therefore, this study developed a new method for treatment of WSSV disease by oral administration of bacterially expressed dsRNA against a novel therapeutic target molecule, which could be a potential candidate strategy for WSSV control in aquaculture.


Asunto(s)
Penaeidae , Virus del Síndrome de la Mancha Blanca 1 , Animales , Virus del Síndrome de la Mancha Blanca 1/genética , ARN Bicatenario/genética , Interferencia de ARN , Penaeidae/genética
5.
J Colloid Interface Sci ; 660: 203-214, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38244489

RESUMEN

Recently, wearable electronic products and gadgets have developed quickly with the aim of catching up to or perhaps surpassing the ability of human skin to perceive information from the external world, such as pressure and strain. In this study, by first treating the cellulosic fiber (modal textile) substrate with (3-aminopropyl) triethoxysilane (APTES) and then covering it with conductive nanocomposites, a bionic corpuscle layer is produced. The sandwich structure of tactile corpuscle-inspired bionic (TCB) piezoresistive sensors created with the layer-by-layer (LBL) technology consists of a pressure-sensitive module (a bionic corpuscle), interdigital electrodes (a bionic sensory nerve), and a PU membrane (a bionic epidermis). The synergistic mechanism of hydrogen bond and coupling agent helps to improve the adhesive properties of conductive materials, and thus improve the pressure sensitive properties. The TCB sensor possesses favorable sensitivity (1.0005 kPa-1), a wide linear sensing range (1700 kPa), and a rapid response time (40 ms). The sensor is expected to be applied in a wide range of possible applications including human movement tracking, wearable detection system, and textile electronics.


Asunto(s)
Nanocompuestos , Silanos , Dispositivos Electrónicos Vestibles , Humanos , Electrónica , Nanocompuestos/química , Textiles
6.
Fish Shellfish Immunol ; 142: 109123, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37813154

RESUMEN

The NF-κB pathway plays an important role in immune regulation. Basigin, an immunoglobulin superfamily membrane protein, is involved in the activation of NF-κB. However, its role in NF-κB signaling in response to pathogen infection remains unclear. In this study, we identified the Basigin gene from Pacific white shrimp, Penaeus vannamei, a representative species for studying the innate immune system of invertebrates. Basigin promoted the degradation of the IκB homolog Cactus, facilitated the nuclear translocation of the NF-κB family member Dorsal, and positively regulated the expression of Dorsal pathway downstream antimicrobial peptide genes. Interestingly, recombinant Basigin protein could bind a variety of Gram-positive and Gram-negative bacteria. Silencing of Basigin inhibited the Dorsal signaling activated by V. parahaemolyticus infection and significantly decreased the survival rate of V. parahaemolyticus-infected shrimp. The expression levels of the antimicrobial peptides ALF1 and ALF2 were downregulated, and the phagocytosis of hemocytes was attenuated in Basigin-silenced shrimp. Similar results were observed in shrimp treated with a recombinant extracellular region of the Basigin protein that was able to compete with endogenous Basigin. Therefore, to the best of our knowledge, this study is the first to demonstrate the function of Basigin as a pathogen recognition receptor that activates NF-κB signaling for antibacterial immunity in shrimp.


Asunto(s)
Penaeidae , Vibrio parahaemolyticus , Virus del Síndrome de la Mancha Blanca 1 , Animales , FN-kappa B/metabolismo , Basigina , Antibacterianos , Proteínas de Artrópodos , Bacterias Gramnegativas , Bacterias Grampositivas , Inmunidad Innata/genética , Vibrio parahaemolyticus/fisiología , Virus del Síndrome de la Mancha Blanca 1/fisiología
7.
Fish Shellfish Immunol ; 139: 108917, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37355218

RESUMEN

The Hippo-Yki signaling pathway plays a crucial role in numerous biological processes. Previous studies have demonstrated the significance of signal transduction components of the Hippo pathway in the immune response of shrimp. In this study, the downstream transcription factor of Hippo signaling, Scalloped, was analyzed in the context of Vibrio parahaemolyticus infection in Pacific white shrimp, Penaeus vannamei. Upon bacterial and fungal infections, the expression of Scalloped was upregulated in hemocytes. Scalloped was found to localize in the nucleus and interact with the Hippo pathway downstream transcriptional co-activator Yki. With the assistance of Yki, Scalloped activated the promoter of Cactus, a cytoplasmic inhibitor of the NF-κB pathway, leading to the inhibition of the nuclear translocation of the NF-κB family member Dorsal in shrimp. By inhibiting the Dorsal pathway, Scalloped reduced the expression of immune functional proteins and negatively regulated the immune response against bacterial infection in shrimp. RNAi-mediated silencing of Scalloped significantly enhanced the survival rate of V. parahaemolyticus-infected shrimp and reduced the bacterial load in tissues. These findings demonstrate the potential of Scalloped as a therapeutic target for vibriosis in crustaceans and contribute to our understanding of the shrimp's antibacterial defense and the functional roles of Hippo signaling in animal immunity.


Asunto(s)
Penaeidae , Vibriosis , Vibrio parahaemolyticus , Animales , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , FN-kappa B/metabolismo , Vía de Señalización Hippo , Vibrio parahaemolyticus/fisiología , Vibriosis/veterinaria , Inmunidad Innata/genética
8.
J Biomater Appl ; 37(10): 1847-1857, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37102311

RESUMEN

Due to the heterogeneity and the complexity of the tumor microenvironment, combination therapy, especially the combination of chemotherapy and photothermal therapy (PTT), had received increasing attention. However, the co-delivery of small molecule drugs for chemotherapy and photothermal agents was a key issue. Herein, we prepared a novel thermo-sensitive hydrogel loading with elemene (ELE)-loaded and nano graphene oxide (NGO)-based liposomes for enhanced combined therapy. ELE was applied as the model drug for chemotherapy because it was a natural sesquiterpene drug with broad-spectrum and efficient antitumor activity. NGO was applied as drug carrier and photothermal agent simultaneously due to its two-dimensional structure and high photo-thermal conversion efficacy. NGO was further modified with glycyrrhetinic acid (GA) to improve its water dispersion, biocompatibility and tumor-targeting ability. ELE was loaded by GA-modified NGO (GA/NGO) to prepare the liposomes designated as ELE-GA/NGO-Lip, which was further mixed with chitosan (CS) solution and ß-glycerin sodium phosphate (ß-GP) solution to prepare the thermo-sensitive hydrogel designated as ELE-GA/NGO-Lip-gel. The obtained ELE-GA/NGO-Lip-gel had the gelling temperature of 37°C, temperature and pH-response gel dissolution and high photo-thermal conversion effect. More importantly, ELE-GA/NGO-Lip-gel upon 808 nm laser irradiation had relative high anti-tumor efficiency against SMMC-7721 cells in vitro. This research might provide a potent platform for the application of thermos-sensitive injectable hydrogel in combined tumor therapy.


Asunto(s)
Neoplasias , Sesquiterpenos , Humanos , Liposomas/química , Hidrogeles/química , Portadores de Fármacos/química , Sesquiterpenos/farmacología , Línea Celular Tumoral , Microambiente Tumoral
9.
Sci Rep ; 13(1): 362, 2023 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-36611055

RESUMEN

Radiation source localization and characterization are challenging tasks that currently require complex analyses for interpretation. Mixed reality (MR) technologies are at the verge of wide scale adoption and can assist in the visualization of complex data. Herein, we demonstrate real-time visualization of gamma ray and neutron radiation detector data in MR using the Microsoft HoloLens 2 smart glasses, significantly reducing user interpretation burden. Radiation imaging systems typically use double-scatter events of gamma rays or fast neutrons to reconstruct the incidence directional information, thus enabling source localization. The calculated images and estimated 'hot spots' are then often displayed in 2D angular space projections on screens. By combining a state-of-the-art dual particle imaging system with HoloLens 2, we propose to display the data directly to the user via the head-mounted MR smart glasses, presenting the directional information as an overlay to the user's 3D visual experience. We describe an open source implementation using efficient data transfer, image calculation, and 3D engine. We thereby demonstrate for the first time a real-time user experience to display fast neutron or gamma ray images from various radioactive sources set around the detector. We also introduce an alternative source search mode for situations of low event rates using a neural network and simulation based training data to provide a fast estimation of the source's angular direction. Using MR for radiation detection provides a more intuitive perception of radioactivity and can be applied in routine radiation monitoring, education & training, emergency scenarios, or inspections.

10.
Microbiol Spectr ; 11(1): e0236322, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36475933

RESUMEN

White spot syndrome virus (WSSV) is a serious threat to shrimp aquaculture, especially Pacific white shrimp, Penaeus vannamei, the most farmed shrimp in the world. Activation of the Hippo-Yki signaling pathway, characterized by the intracellular Hippo-Wts kinase cascade reactions and the phosphorylation and cytoplasmic retention of Yki, is widely involved in various life activities. The current work established the fundamental structure and signal transduction profile of the Hippo-Yki pathway in P. vannamei and further investigated its role in viral infection. We demonstrated that WSSV promoted the dephosphorylation and nuclear translocation of Yki, suggesting that Hippo signaling is impaired and Yki is activated after WSSV infection in shrimp. In vivo, Yki gene silencing suppressed WSSV infection, while Hippo and Wts silencing promoted it, indicating a positive role of Hippo signaling in antiviral response. Further analyses showed that Yki suppressed Dorsal pathway activation and inhibited hemocyte apoptosis in WSSV-infected shrimp, while Hippo and Wts showed opposite effects, which contributed to the role of Hippo signaling in WSSV infection. Therefore, the current study suggests that WSSV annexes Yki to favor its infection in shrimp by inhibiting Hippo signaling. IMPORTANCE White spot syndrome virus (WSSV) is one of the most harmful viral pathogens to shrimp. The pathological mechanism of WSSV infection remains unclear to date. The Hippo-Yki signaling pathway is important for various biological processes and is extensively involved in mammalian immunity, but little is known about its role in infectious diseases in invertebrates. Based on revealing the fundamental structure of the shrimp Hippo pathway, this study investigated its implication in the pathogenesis of WSSV disease. We demonstrated that WSSV enhanced Yki activation by inhibiting Hippo signaling in shrimp. The activated Yki promoted WSSV infection by inhibiting hemocyte apoptosis and suppressing the activation of Dorsal, an NF-κB family member in shrimp that is critical for regulating antiviral response. Therefore, this study suggests that WSSV can hijack the Hippo-Yki signaling pathway to favor its infection in shrimp.


Asunto(s)
Penaeidae , Virus del Síndrome de la Mancha Blanca 1 , Animales , Vía de Señalización Hippo , Virus del Síndrome de la Mancha Blanca 1/fisiología , Transducción de Señal , Antivirales , Mamíferos
11.
Opt Express ; 30(15): 27381-27394, 2022 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-36236910

RESUMEN

Lattice light-sheet microscopy (LLSM) is promising in long-term biological volumetric imaging due to its high spatiotemporal resolution and low phototoxicity. However, three-dimensional (3D) isotropic spatial resolution remains an unmet goal in LLSM because of its poorer axial resolution. Combing LLSM with fluorescence differential detection, namely LLSDM, has been proposed to improve the axial resolution of LLSM in simulation. It demonstrates the possibility of further enhancing the axial resolution in 3D volumetric imaging with LLSM by specifically discarding the off-focus photons captured using a complementary optical lattice (OL) profile generated with additional 0-π phase modulation at the objective pupil plane. The direct generation of the complementary lattice profile using the binary phase modulator conjugated to the sample plane for amplitude modulation, as used in LLSM, is also permittable. Nevertheless, the previously proposed configuration fails to provide a symmetric complementary lattice pattern along the axial axis, thus leading to the imbalanced off-focus photon suppression in the reconstructed images after subtraction [Opt. Lett.45, 2854 (2020)10.1364/OL.393378]. Here, we modified the LLSDM theory which can produce an ideal complementary lattice pattern with central zero intensity and symmetrically distributed sidelobes. We also analyzed the impact of numerical aperture matching between the original and complementary lattice patterns and presented the consistency between the simulated and experimental results. As demonstrated by imaging the distribution of fluorescent beads and microtubules in fixed U2OS cells, as well as the dynamics of filopodia in live U2OS cells, LLSDM provides about 1.5 times improvement in axial resolution, and higher imaging contrast compared with traditional LLSM.


Asunto(s)
Microscopía , Microtúbulos , Microscopía/métodos
12.
Int J Mol Sci ; 23(19)2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36233199

RESUMEN

In the Hippo pathway, activation of Hippo and Warts (Wts) kinases results in the phosphorylation of Yorkie (Yki), to prevent its nuclear translocation. Shrimp aquaculture is threatened by Vibrio genus bacteria. In this study, we examine the role of the Hippo pathway in immune defense against Vibrio parahaemolyticus in Pacific white shrimp Penaeus vannamei. We show that V. parahaemolyticus infection promotes the expression of Yki and facilitates the dephosphorylation and nuclear translocation of Yki, indicating the inhibition of Hippo signaling upon bacterial infection. There is a complex regulatory relationship between the Hippo pathway components Hippo, Wts, and Yki and the immune-related transcription factors Dorsal, Relish, and STAT. Silencing of Hippo and Wts weakened hemocyte phagocytosis, while the silencing of Yki enhanced it, suggesting a positive regulation of shrimp cellular immunity by Hippo signaling activation. In vivo silencing of Hippo and Wts decreased the survival rates of V. parahaemolyticus-infected shrimp and elevated the bacterial content in tissues, while the silencing of Yki showed the opposite results. This suggests that the activation of Hippo signaling and the inhibition of Yki enhance antibacterial immunity in shrimp.


Asunto(s)
Penaeidae , Vibriosis , Vibrio parahaemolyticus , Animales , Inmunidad , Penaeidae/inmunología , Penaeidae/microbiología , Transducción de Señal , Factores de Transcripción/metabolismo , Vibriosis/veterinaria
13.
Acta Biochim Biophys Sin (Shanghai) ; 54(10): 1421-1430, 2022 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-36148947

RESUMEN

Egg granuloma formation in the liver is the main pathological lesion caused by Schistosoma japonicum infection, which generally results in liver fibrosis and may lead to death in advanced patients. MicroRNAs (miRNAs) regulate the process of liver fibrosis, but the putative function of miRNAs in liver fibrosis induced by S. japonicum infection is largely unclear. Here, we detect a new miRNA, miR-182-5p, which shows significantly decreased expression in mouse livers after stimulation by soluble egg antigen (SEA) of S. japonicum or S. japonicum infection. Knockdown or overexpression of miR-182-5p in vitro causes the increased or decreased expression of tristetraprolin (TTP), an important immunosuppressive protein in the process of liver fibrosis. Furthermore, knockdown of miR-182-5p in vivo upregulates TTP expression and significantly alleviates S. japonicum-induced hepatic fibrosis. Our data demonstrate that downregulation of miR-182-5p increases the expression of TTP in mouse livers following schistosome infection, which leads to destabilization of inflammatory factor mRNAs and attenuates liver fibrosis. Our results uncover fine-tuning of liver inflammatory reactions related to liver fibrosis caused by S. japonicum infection and provide new insights into the regulation of schistosomiasis-induced hepatic fibrosis.


Asunto(s)
MicroARNs , Schistosoma japonicum , Animales , Ratones , Schistosoma japonicum/genética , Schistosoma japonicum/metabolismo , Tristetraprolina/genética , Tristetraprolina/metabolismo , Cirrosis Hepática/genética , Hígado/metabolismo , MicroARNs/genética , MicroARNs/metabolismo
14.
Fish Shellfish Immunol ; 127: 187-194, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35716970

RESUMEN

The kelch motif-containing proteins are widely present in organisms and known to be involved in various biological processes, but their roles in immunity remain unclear. In this study, a kelch motif-containing protein KLHDC2 was identified from Pacific white shrimp Penaeus vannamei and its immune function was investigated. The klhdc2 gene was widely expressed in shrimp tissues and its protein product was mainly present in the nucleus. Expression of klhdc2 was regulated by shrimp NF-κB family members Dorsal and Relish, and changed after immune stimulation. KLHDC2 could enhance the immune defense against Vibrio parahaemolyticus in shrimp but inhibit that against white spot syndrome virus (WSSV). Further analyses showed that KLHDC2 did not affect the phagocytosis of hemocytes but regulated the expression of a series of immune effector genes. KLHDC2 has a complex regulatory relationship with Dorsal and Relish, which may partly contribute to its positive role in antibacterial response by regulating humoral immunity. Moreover, the regulatory effect of KLHDC2 on WSSV ie1 gene contributed to its negative effect on antiviral response. Therefore, the current study enrichs the knowledge on the Kelch family and helps to learn more about the regulatory mechanism of shrimp immunity.


Asunto(s)
Penaeidae , Vibrio parahaemolyticus , Virus del Síndrome de la Mancha Blanca 1 , Animales , Proteínas de Artrópodos , Inmunidad Innata/genética , Secuencia Kelch , Fagocitosis , Vibrio parahaemolyticus/fisiología , Virus del Síndrome de la Mancha Blanca 1/fisiología
15.
Dev Comp Immunol ; 133: 104411, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35447159

RESUMEN

The Wnt family genes are essentially implicated in development and growth in animals. Accumulating clues have pointed to the importance of Wnts in invertebrate immunity, but the underlying mechanisms are still unclear to date. The Wnt5b has been known to promote white spot syndrome virus (WSSV) infection in shrimp but its role in antibacterial response remains unclear. In the current study, we focused on the involvement of Wnt5b in Vibrio parahaemolyticus infection in Pacific white shrimp Penaeus vannamei. We demonstrated that the expression of Wnt5b was regulated by the IMD-Relish and JAK-STAT pathways but not the Dorsal pathway and was suppressed upon bacterial infection. Although Wnt5b did not affect the cellular immunity in shrimp, it was involved in regulation of humoral immunity. Silencing of Wnt5b in vivo significantly increased expression of several antimicrobial peptides but decreased that of many immune functional proteins including C-type lectins and lysozymes. Treatment with recombinant Wnt5b protein increased the susceptibility of shrimp to V. parahaemolyticus infection, while silencing of Wnt5b in vivo showed an opposite result. These suggested that Wnt5b plays a negative role in antibacterial response in shrimp. Together with previous reports, the current study shows that Wnt5b functions as an inhibitor for shrimp immunity, which is a potential target for improving immune responses against infection.


Asunto(s)
Penaeidae , Vibrio parahaemolyticus , Virus del Síndrome de la Mancha Blanca 1 , Animales , Antibacterianos/metabolismo , Proteínas de Artrópodos/metabolismo , Inmunidad Innata/genética , Virus del Síndrome de la Mancha Blanca 1/fisiología
16.
Front Immunol ; 12: 697071, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34745088

RESUMEN

Background: High mobility group box 1 (HMGB1) causes microvascular endothelial cell barrier dysfunction during acute lung injury (ALI) in sepsis, but the mechanisms have not been well understood. We studied the roles of RAGE and Rho kinase 1 (ROCK1) in HMGB1-induced human pulmonary endothelial barrier disruption. Methods: In the present study, the recombinant human high mobility group box 1 (rhHMGB1) was used to stimulate human pulmonary microvascular endothelial cells (HPMECs). The endothelial cell (EC) barrier permeability was examined by detecting FITC-dextran flux. CCK-8 assay was used to detect cell viability under rhHMGB1 treatments. The expression of related molecules involved in RhoA/ROCK1 pathway, phosphorylation of myosin light chain (MLC), F-actin, VE-cadherin and ZO-1 of different treated groups were measured by pull-down assay, western blot and immunofluorescence. Furthermore, we studied the effects of Rho kinase inhibitor (Y-27632), ROCK1/2 siRNA, RAGE-specific blocker (FPS-ZM1) and RAGE siRNA on endothelial barrier properties to elucidate the related mechanisms. Results: In the present study, we demonstrated that rhHMGB1 induced EC barrier hyperpermeability in a dose-dependent and time-dependent manner by measuring FITC-dextran flux, a reflection of the loss of EC barrier integrity. Moreover, rhHMGB1 induced a dose-dependent and time-dependent increases in paracellular gap formation accompanied by the development of stress fiber rearrangement and disruption of VE-cadherin and ZO-1, a phenotypic change related to increased endothelial contractility and endothelial barrier permeability. Using inhibitors and siRNAs directed against RAGE and ROCK1/2, we systematically determined that RAGE mediated the rhHMGB1-induced stress fiber reorganization via RhoA/ROCK1 signaling activation and the subsequent MLC phosphorylation in ECs. Conclusion: HMGB1 is capable of disrupting the endothelial barrier integrity. This study demonstrates that HMGB1 activates RhoA/ROCK1 pathway via RAGE, which phosphorylates MLC inducing stress fiber formation at short time, and HMGB1/RAGE reduces AJ/TJ expression at long term independently of RhoA/ROCK1 signaling pathway.


Asunto(s)
Permeabilidad Capilar/fisiología , Células Endoteliales/metabolismo , Proteína HMGB1/fisiología , Receptor para Productos Finales de Glicación Avanzada/fisiología , Quinasas Asociadas a rho/fisiología , Células Cultivadas , Humanos , Cadenas Ligeras de Miosina/fisiología , Transducción de Señal/fisiología
17.
Dev Comp Immunol ; 114: 103826, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32784011

RESUMEN

The LARK proteins containing a C2HC-type zinc finger motif and two RNA recognition motifs are conserved across vertebrates and invertebrates. Previous studies have suggested that invertebrate LARKs and their mammalian counterparts, the RBM4 proteins, regulate gene expression by affecting RNA stability and post-transcriptional processing, participating in multiple life processes. In the current study, the LARK gene from Pacific white shrimp Litopenaeus vannamei was identified and functionally explored in the context of immunity. The LARK protein was mainly present in the nucleus of its expression vector-transfected S2 cells, and the LARK mRNA was detectable in all the tested shrimp tissues. Expression of LARK in gill was up-regulated by immune stimulation with various pathogens. In vivo experiments demonstrated that LARK played positive roles in both antiviral and antibacterial responses and silencing of LARK could make shrimp more susceptible to infection with Vibrio parahaemolyticus and white spot syndrome virus (WSSV). Although silencing of LARK did not affect the phagocytic activity of hemocytes, it regulated expression of many components of the NF-κB and JAK-STAT pathways and a series of immune function proteins. These suggested that LARK could be mainly involved in regulation of humoral immunity. The current study could help reveal the roles of LARK/RBM4 in immunity and further explore the regulatory mechanisms of shrimp immunity.


Asunto(s)
Proteínas de Artrópodos/genética , Núcleo Celular/metabolismo , Infecciones por Virus ADN/inmunología , Branquias/metabolismo , Hemocitos/fisiología , Penaeidae/inmunología , Proteínas de Unión al ARN/genética , Vibriosis/inmunología , Vibrio parahaemolyticus/fisiología , Virus del Síndrome de la Mancha Blanca 1/fisiología , Animales , Proteínas de Artrópodos/metabolismo , Proteínas de Drosophila/genética , Silenciador del Gen , Inmunidad Humoral , FN-kappa B/metabolismo , Transporte de Proteínas , Proteínas de Unión al ARN/metabolismo , Transducción de Señal , Regulación hacia Arriba
18.
Nanomaterials (Basel) ; 10(12)2020 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-33291508

RESUMEN

Angular momentums (AMs) of photons are crucial physical properties exploited in many fields such as optical communication, optical imaging, and quantum information processing. However, the active manipulation (generation, switching, and conversion) of AMs of light on a photonic chip remains a challenge. Here, we propose and numerically demonstrate a reconfigurable graphene-based hybrid plasmonic waveguide (GHPW) with multiple functions for on-chip AMs manipulation. Its physical mechanism lies in creating a switchable phase delay of ±π/2 between the two orthogonal and decomposed linear-polarized waveguide modes and the spin-orbit coupling in the GHPW. For the linear-polarized input light with a fixed polarization angle of 45°, we can simultaneously switch the chirality (with -ћ/+ћ) of the transverse component and the spirality (topological charge ℓ = -1/+1) of the longitudinal component of the output terahertz (THz) light. With a switchable phase delay of ±π in the GHPW, we also developed the function of simultaneous conversion of the charity and spirality for the circular-polarized input light. In addition, a selective linear polarization filtering with a high extinction ratio can be realized. With the above multiple functions, our proposed GHPWs are a promising platform in AMs generation, switching, conversion, and polarization filtering, which will greatly expand its applications in the THz photonic integrated circuits.

19.
ACS Omega ; 4(12): 15097-15100, 2019 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-31552353

RESUMEN

The semi-transparent solar cells are promising to be applied in building integrated photovoltaic (BIPV) and tandem solar cells. In this study, we fabricate semi-transparent and stable solar cells for BIPV by utilizing a poly (ethylene oxide) electrolyte and controlling the size of TiO2 nanoparticles and the thickness of the TiO2 film. The power conversion efficiency of the semi-transparent (over 50% transmittance at 620-750 nm) and quasi-solid solar cells is 5.78% under standard AM1.5G, 100 mW cm-2. The higher conductivity and smaller diffusion resistance of the quasi-solid electrolyte inside the mesoporous TiO2 film indicate the confinement effects of the polymer electrolyte inside a mesoporous TiO2 film. The unsealed semi-transparent and quasi-solid solar cell retains its initial efficiency during 1000 h irradiation in humid air.

20.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(7): 842-846, 2019 Jul.
Artículo en Chino | MEDLINE | ID: mdl-31441407

RESUMEN

OBJECTIVE: To observe the damage of high mobility group box 1 (HMGB1) on human umbilical vein endothelial cell (HUVEC) barrier permeability and the protective effect of unfractionated heparin (UFH), and to explore the down-regulated protection effect mechanism of UFH on HMGB1-mediated vascular endothelial cadherin (VE-cadherin) expression. METHODS: The trypsin-digested HUVEC were subcultured in culture flasks. When the cells were grown to 80%, they were randomly divided into four groups: phosphate buffer (PBS) control group (200 µL PBS), recombinant human high mobility group box 1 (rhHMGB1) treatment group (100 µg/L rhHMGB1), UFH control group (10 kU/L UFH), and UFH pretreatment group (10 kU/L UFH+100 µg/L rhHMGB1). The cells in each group were challenged with different reagent for 24 hours, and the activity of endothelial cells was determined by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The permeability of endothelial cells was measured by Transwell method, and the expression and distribution of VE-cadherin was observed by immunofluorescence. The protein expressions of VE-cadherin and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) were determined by Western Blot. RESULTS: After treatment with 100 µg/L rhHMGB1 for 24 hours, the activity of endothelial cells was not significantly different from that of the PBS control group (A value: 0.230±0.004 vs. 0.255±0.006, P > 0.05), but the permeability was significantly increased (glucan FD40 fluorescence intensity: 11.05±0.12 vs. 6.34±0.39, P < 0.05). Compared with PBS control group, the fluorescence microscopy showed that the VE-cadherin membrane localization was reduced, the distribution was loose, and there were obvious fissures between cells in rhHMGB1 treatment group, and quantitative analysis showed the protein expression of VE-cadherin was decreased significantly (VE-cadherin/ß-actin: 0.16±0.04 vs. 0.31±0.03, P < 0.05), and the expression of p-p38MAPK protein was significantly increased (p-p38MAPK/ß-actin: 0.79±0.03 vs. 0.26±0.05, P < 0.05). UFH pretreatment could protect HMGB1-mediated endothelial cell injury, cell permeability was significantly reduced (glucan FD40 fluorescence intensity: 9.11±0.23 vs. 11.05±0.12), fluorescence expression of VE-cadherin was enhanced, membrane localization was significantly increased, quantitative analysis showed that VE-cadherin protein expression was significantly up-regulated (VE-cadherin/ß-actin: 0.24±0.02 vs. 0.16±0.04), and p38MAPK phosphorylation level was significantly decreased (p-p38MAPK/ß-actin: 0.54±0.05 vs. 0.79±0.03), the difference was statistically significant as compared with rhHMGB1 treatment group (all P < 0.05). There was no significant difference in all parameters between PBS control group and UFH control group. CONCLUSIONS: UFH can protect the endothelial cell barrier from the HMGB1 by regulating the expression and distribution of VE-cadherin. The mechanism may be related to the inhibition of p38MAPK phosphorylation by UFH.


Asunto(s)
Cadherinas/metabolismo , Fibrinolíticos/uso terapéutico , Proteína HMGB1/metabolismo , Heparina/uso terapéutico , Antígenos CD/metabolismo , Permeabilidad Capilar , Células Cultivadas , Células Endoteliales , Humanos
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