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Background: B7-H3 (or CD276) represents an important costimulatory molecule expressed in many malignant solid tumors, including colorectal cancer (CRC). The receptor of B7-H3 is not known, and the intracellular function of B7-H3 remains obscure. Herein, we report that B7-H3 upregulated the epidermal growth factor heparin-binding epidermal growth factor (HB-EGF), likely by regulating hypoxia-inducible factor 1α (HIF-1α) and thereby promoting the progression of CRC. Methods: Lentiviral transfection was performed on CRC cells to establish stable low-B7-H3 expression cells. A mechanistic analysis with an Agilent human gene expression profiling chip was conducted on them. Clinical data and specimens were collected to detect the connection between B7-H3 and HB-EGF in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the messenger RNA (mRNA) level of B7-H3, HB-EGF, and HIF-1α. Chromatin immunoprecipitation (ChIP) quantitative real-time PCR was conducted. The protein level of HIF-1α and the phosphatidylinositide 3-kinases (PI3K)-protein kinase B (AKT) pathway were detected by western blot. HIF-1α was recovered by lentiviral transfection, and the HB-EGF mRNA levels, proliferation, invasion, and angiogenesis ability were detected. Results: B7-H3 promoted tumor progression through HB-EGF and the PI3K-AKT pathway. As B7-H3 was downregulated, HB-EGF levels were significantly reduced simultaneously, a growth trend that was shown by both CRC cell lines and cancer tissues. In addition, B7-H3 and HB-EGF had significant associations with tumor-node-metastasis (TNM) stage and lymph node metastasis in 50 CRC patients. The binding ability of HIF-1α to the HB-EGF promoter region was significantly decreased in the shB7-H3 RKO group. Western blot revealed that PI3K, AKT, and mammalian target of rapamycin (mTOR) protein amounts and p-AKT and p-mTOR phosphorylation were also downregulated in shB7-H3 RKO cells, suggesting that B7-H3 may regulate HIF-1α via PI3K-AKT signaling. After recovery of the HIF-1α level by lentiviral transfection, the HB-EGF mRNA levels, proliferation, invasion, and angiogenesis in CRC cells recovered as well. Conclusions: B7-H3 may transmit intracellular signals through PI3K-AKT-mTOR-HIF-1α signaling, upregulating HB-EGF. As the final transcription factor of the pathway, HIF-1α regulates the transcription of the HB-EGF gene, thereby promoting HB-EGF expression, which eventually mediates cell proliferation, invasion, and angiogenesis and promotes the progression of CRC.
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Spinal cord injury (SCI) often results in motor and sensory deficits, or even paralysis. Due to the role of the cascade reaction, the effect of excessive reactive oxygen species (ROS) in the early and middle stages of SCI severely damage neurons, and most antioxidants cannot consistently eliminate ROS at non-toxic doses, which leads to a huge compromise in antioxidant treatment of SCI. Selenium nanoparticles (SeNPs) have excellent ROS scavenging bioactivity, but the toxicity control problem limits the therapeutic window. Here, we propose a synergistic therapeutic strategy of SeNPs encapsulated by ZIF-8 (SeNPs@ZIF-8) to obtain synergistic ROS scavenging activity. Three different spatial structures of SeNPs@ZIF-8 were synthesized and coated with ferrostatin-1, a ferroptosis inhibitor (FSZ NPs), to achieve enhanced anti-oxidant and anti-ferroptosis activity without toxicity. FSZ NPs promoted the maintenance of mitochondrial homeostasis, thereby regulating the expression of inflammatory factors and promoting the polarization of macrophages into M2 phenotype. In addition, the FSZ NPs presented strong abilities to promote neuronal maturation and axon growth through activating the WNT4-dependent pathways, while prevented glial scar formation. The current study demonstrates the powerful and versatile bioactive functions of FSZ NPs for SCI treatment and offers inspiration for other neural injury diseases.
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Antioxidantes , Nanopartículas , Espécies Reativas de Oxigênio , Selênio , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Nanopartículas/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Selênio/farmacologia , Neurônios/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Ratos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células RAW 264.7 , Regeneração Nervosa/efeitos dos fármacosRESUMO
This article conducts a comprehensive study on the activation characteristics of faults in the mine and analyzes the distribution patterns of the original rock stress field. Through quantitative research and analysis, we determine the partitioning characteristics of tectonic stress in the mine field under the dual effects of fault activation and original rock stress. The study also reveals the significant impact of different fault activation characteristics and different tectonic stress partitions on the stability of roadway surrounding rock. Using the Mohr-Coulomb strength criterion as a foundation, we investigate the mechanisms of fault activation and establish a mathematical model for fuzzy comprehensive evaluation. This model enables us to determine the strength level of fault activation in coal seam 9 of the Limin coal mine and construct a geological structure model. It has realized the transformation of fault activation degree from qualitative evaluation to quantitative evaluation. The stress state analysis software is used to draw the division of tectonic stress dangerous areas under the synergistic effect of fault activation and original rock stress. We then analyze the impact on the stability of roadway surrounding rock in these different hazardous areas. Utilizing the fuzzy comprehensive evaluation method, we take into account the impact of faults on the distribution characteristics of stress fields and the stability of roadway surrounding rock. This approach enables us to more accurately and comprehensively determine the hazardous areas of tectonic stress in the mine field under the dual effects of faults and original rock stress.
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Bone defects resulting from severe trauma, tumors, inflammation, and other factors are increasingly prevalent. Stem cell-based therapies have emerged as a promising alternative. Dental pulp stem cells (DPSCs), sourced from dental pulp, have garnered significant attention owing to their ready accessibility and minimal collection-associated risks. Ongoing investigations into DPSCs have revealed their potential to undergo osteogenic differentiation and their capacity to secrete a diverse array of ontogenetic components, such as extracellular vesicles and cell lysates. This comprehensive review article aims to provide an in-depth analysis of DPSCs and their secretory components, emphasizing extraction techniques and utilization while elucidating the intricate mechanisms governing bone regeneration. Furthermore, we explore the merits and demerits of cell and cell-free therapeutic modalities, as well as discuss the potential prospects, opportunities, and inherent challenges associated with DPSC therapy and cell-free therapies in the context of bone regeneration.
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Interleukin-37 (IL-37) has been shown to inhibit tumor growth in various cancer types. However, the immune regulatory function of IL-37 in the tumor microenvironment is unclear. Here, we established a human leukocyte antigen-I (HLA-I)-matched humanized patient-derived xenograft hepatocellular carcinoma (HCC) model and three murine orthotopic HCC models to study the function of IL-37 in the tumor microenvironment. We found that IL-37 inhibited HCC growth and promoted T cell activation. Further study revealed that IL-37 impaired the immunosuppressive capacity of myeloid-derived suppressor cells (MDSCs). Pretreatment of MDSCs with IL-37 before adoptive transfer attenuated their tumor-promoting function in HCC tumor-bearing mice. Moreover, IL-37 promoted both glycolysis and oxidative phosphorylation in MDSCs, resulting in the upregulation of ATP release, which impaired the immunosuppressive capacity of MDSCs. Collectively, we demonstrated that IL-37 inhibited tumor development through dampening MDSCs' immunosuppressive capacity in the tumor microenvironment via metabolic reprogramming, making it a promising target for future cancer immunotherapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Supressoras Mieloides , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Reprogramação Metabólica , Microambiente TumoralRESUMO
Histidine (His) and its metabolite analysis is significant due to their vital roles in the diagnosis of diseases. In practical applications, simple and effective detection and discrimination of these metabolic species are still a great challenge due to their highly similar structures. Herein, photoluminescence (PL)-electrochemiluminescence (ECL) dual-mode sensor arrays consisting of a series of sensing elements were proposed for simultaneous quantitation and accurate discrimination of His and its four key metabolites (including histamine, imidazole-4-acetic acid, N-acetylhistamine, and imidazole propionate). The sensing elements of these sensor arrays were constructed by employing two solvent iridium(III) complexes ([Ir(pbz)2(DMSO)Cl] and [Ir(ppy)2(DMSO)Cl], pbz = 3-(2-pyridyl)benzoic acid, ppy = 2-phenylpyridine) with excellent PL and ECL performances as cross-responsive sensing units. Based on diverse coordination abilities of the two complexes with the imidazole group of the five targets, PL and ECL responses of each sensing unit can be enhanced to various degrees, which generate unique fingerprint patterns for the corresponding targets. Through principal component analysis, the multifarious patterns (two-, three-, and four-element sensor arrays) can be transformed into simple visualization modes, from which His and its four key metabolites can be effectively discriminated against each other. Moreover, the quantitation of an individual metabolic species at different concentrations and the recognition of the mixtures with different ratios were also accurately achieved. Notably, His and its four key metabolites in urine can also be successfully discriminated by the as-fabricated sensor arrays, and the patients with kidney diseases can be identified clearly, providing a promising way for disease diagnosis.
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Dimetil Sulfóxido , Histidina , Humanos , Fotometria , Medições LuminescentesRESUMO
In order to study the mining pressure characteristics of the shallow buried coal seam with the same silo working face under the very close mining void zone and the overlying coal rock body, the theoretical analysis is used to determine whether the open-cutting eye bearing layer belongs to the mining under the very close mining void zone or not, based on the numerical simulation of FLAC3D and on-site measurement of the working resistance at the end of the cycle of the working face's hydraulic bracket, It is proposed to divide the mining stress of the working face based on the advancing length of the working face, that is, the high-pressure zone, the transition zone and the low-pressure zone. The results of the study show that: FLAC3D software was used to analyze the stress intensity of the "C" island working face when it was mined back to 50 m, 100 m, 150 m, and 180 m (one time "square"), and the simulation results were imported into the Origin software, which was used to analyze the stress intensity of the working face. The simulation results were imported into Origin software, and the influence range of mining stress was divided into four areas: high-stress area, stress transition area, low-stress area, and "square" stress concentration area. According to the on-site measurement of the working resistance at the end of hydraulic support cycle, the initial pressure step of the working face under the overlying coal rock body is 48.9-55.7 m, with the peak value of 38 MPa, the cycle pressure step is 9.0-23.3 m, with the peak value of 36 MPa, and the dynamic load factor of the working face is 1.14-1.16; relative to the overlying coal rock body, the average decrease of the cycle pressure step is nearly 10% and the average increase of dynamic load factor is 1.14-1.16; compared with that under the overlying coal rock body, the average decrease of the cycle pressure step is nearly 10% and the average increase of dynamic load factor is 1.14-1.16. Compared with the overlying coal rock body, the average decrease of the cycle pressure step under the overlying mining zone is nearly 10%, the average increase of the dynamic load factor is 20%, and there is no obvious regularity and periodicity in the direction of strike, and the working face is divided into three parts along the direction of strike: high-pressure zone, transition zone, and low-pressure zone. Therefore, in the process of mining under the overlying coal rock body, we should strengthen the roadway peripheral rock support and roof and floor management, which is of guiding significance to the mining of similar working faces and mine safety production.
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In recent years, the number of traffic accidents caused by road defects has increased dramatically all over the world, and the repair and prevention of road defects is an urgent task. Researchers in different countries have proposed many models to deal with this task, but most of them are either highly accurate and slow in detection, or the accuracy is low and the detection speed is high. The accuracy and speed have achieved good results, but the generalization of the model to other datasets is poor. Given this, this paper takes YOLOv5s as a benchmark model and proposes an optimization model to solve the problem of road defect detection. First, we significantly reduce the parameters of the model by pruning the model and removing unimportant modules, propose an improved Spatial Pyramid Pooling-Fast (SPPF) module to improve the feature signature fusion ability, and finally add an attention module to focus on the key information. The activation function, sampling method, and other strategies were also replaced in this study. The test results on the Global Road Damage Detection Challenge (GRDDC) dataset show that the FPS of our proposed model is not only faster than the baseline model but also improves the MAP by 2.08%, and the size of this model is also reduced by 6.07 M.
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Abscesso Abdominal , Esplenopatias , Humanos , Abscesso Abdominal/diagnóstico por imagem , Abscesso Abdominal/etiologia , Abscesso/diagnóstico por imagem , Abscesso/cirurgia , Erros de Diagnóstico , Esplenopatias/diagnóstico por imagem , Esplenopatias/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
γδT cells are promising candidates for cellular immunotherapy due to their immune regulation through cytokine production and MHC-independent direct cytotoxicity against a broad spectrum of tumors. However, current γδT cell-based cancer immunotherapy has limited efficacy, and novel strategies are needed to improve clinical outcomes. Here, we report that cytokine pretreatment with IL12/18, IL12/15/18, IL12/18/21, and IL12/15/18/21 effectively enhanced the activation and cytotoxicity of in vitro-expanded murine and human γδT cells. However, only adoptive transfer of IL12/18/21 preactivated γδT cells significantly inhibited tumor growth in a murine melanoma model and a hepatocellular carcinoma model. Both IL12/18/21 preactivated antibody-expanded and zoledronate-expanded human γδT cells effectively controlled tumor growth in a humanized mouse model. IL12/18/21 preactivation promoted γδT cell proliferation and cytokine production in vivo and enhanced IFNγ production and activation of endogenous CD8+ T cells in a cell-cell contact- and ICAM-1-dependent manner. Furthermore, the adoptive transfer of IL12/18/21 preactivated γδT cells could overcome the resistance to anti-PD-L1 therapy, and the combination therapy had a synergistic effect on the therapeutic outcomes. Moreover, the enhanced antitumor function of adoptively transferred IL12/18/21 preactivated γδT cells was largely diminished in the absence of endogenous CD8+ T cells when administered alone or in combination with anti-PD-L1, suggesting a CD8+ T cell-dependent mechanism. Taken together, IL12/18/21 preactivation can promote γδT cell antitumor function and overcome the resistance to checkpoint blockade therapy, indicating an effective combinational cancer immunotherapeutic strategy.
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Neoplasias , Humanos , Camundongos , Animais , Linfócitos T CD8-Positivos , Imunoterapia , Citocinas , Interleucina-12 , Antígeno B7-H1RESUMO
Rehydrated sea cucumber (RSC) is a popular seafood in northeast Asia with high deep-processing potential. Yet the development of value-added RSC product is limited by non-enzymatic decrosslinking of RSC collagen hydrogel system, which could potentially be solved by crosslinking enhancement. In this work, NaIO4 oxidized inositol (NOXIN), a novel crosslinker, was synthesized and its capacity in RSC stabilization was evaluated with texture profile analysis, free amino group content, total soluble protein, water activity, water withholding capacity and scanning electron microscope (SEM). The results show that NOXIN could stabilize RSC in a dose dependent manner by crosslinking the amino groups on collagen, thus enhances the mechanical strength and water holding capacity, retains water activity, and suppresses protein degradation of the hydrogel system, although overdosing compromises the stabilizing effect. The results of this study have not only validated the capacity of NOXIN as protein crosslinker, but also provided reference to the development of new crosslinkers.
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Pepinos-do-Mar , Animais , Inositol , Oxirredução , Hidrogéis , ÁguaRESUMO
BACKGROUND: This study sought to investigate the inhibitory effect of pre-gelatinized dialdehyde starch (P-DAS) on the deterioration of sea cucumber during high-temperature sterilization. RESULTS: It was found that pre-gelatinization reduced crystallinity and average molecular weight of dialdehyde starch (DAS), exposed free aldehyde groups, improved the solubility, and unified the particle sizes. According to the texture profiles of sea cucumber, the crosslinking power of P-DAS was higher than that of DAS. The results of free amino content, total soluble substance, water retention, water distribution, relaxation time and scanning electron microscopy all showed that the crosslinking effect was dose-dependent on crosslinking agent. CONCLUSION: These results have proved that large molecules such as P-DAS, when properly handled, could also efficiently enter collagen hydrogels and perform crosslinking, providing reference for the development of new protein food stabilizing agents. © 2022 Society of Chemical Industry.
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Temperatura Alta , Pepinos-do-Mar , Animais , Amido/química , ColágenoRESUMO
Background: Colon adenocarcinoma (COAD) is a common malignant tumor of the digestive tract with poor clinical outcomes. Cuproptosis is a novel cell death mechanism and linked to mitochondrial respiration. However, the role of cuproptosis in colon cancer tumor microenvironment (TME) and immune responses remains unknown. Methods: We conducted difference analysis to identify the differential expressed cuproptosis-related genes (CRGs). According to the CRGs, the TCGA-COAD samples were categorized using consensus clustering. The LASSO regression analysis was utilized to develop the cuproptosis-related signature. We then verified the model reliability by Kaplan-Meier, PCA, and ROC analysis. The GES39582 cohort served as the validation set. GO and KEGG functional analyses were conducted to investigate the underlying mechanism. We compared the infiltration levels of immune cells, the expression levels of immune checkpoints, and microsatellite instability (MSI) status between the high- and low-risk groups. Additionally, the relationships between the risk signature and immune cells and cancer stem cell (CSC) were analyzed. Results: Finally, we identified 9 differentially expressed CRGs in COAD. According to the expression of CRGs, the TCGA-COAD samples were separated into two clusters. The 11-gene signature was established by LASSO, and it had excellent predictive power for COAD prognosis. Besides, we used the GSE39582 cohort to validate the prognostic value of the model. GO and KEGG results demonstrated that the survival differences between two risk groups was mainly linked to the extracellular matrix (ECM). Further immune characterization analysis showed the significant differences in the immune cell infiltration and immune responses between two risk groups. Conclusion: Overall, the novel cuproptosis-related signature was able to accurately predict COAD prognosis and played important roles in COAD tumor microenvironment and immune responses.
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Mosquito saliva proteins modulate the human immune and hemostatic systems and control mosquito-borne pathogenic infections. One mechanism through which mosquito proteins may influence host immunity and hemostasis is their interactions with key human receptor proteins that may act as receptors for or coordinate attacks against invading pathogens. Here, using pull-down assays and proteomics-based mass spectrometry, we identified 11 Ae. aegypti salivary gland proteins (SGPs) (e.g., apyrase, Ae. aegypti venom allergen-1 [AaVA-1], neutrophil stimulating protein 1 [NeSt1], and D7 proteins), that interact with one or more of five human receptor proteins (cluster of differentiation 4 [CD4], CD14, CD86, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN], and Toll-like receptor 4 [TLR4]). We focused on CD4- and DC-SIGN-interacting proteins and confirmed that CD4 directly interacts with AaVA-1, D7, and NeST1 recombinant proteins and that AaVA-1 showed a moderate interaction with DC-SIGN using ELISA. Bacteria responsive protein 1 (AgBR1), an Ae. aegypti saliva protein reported to enhance ZIKV infection in humans but that was not identified in our pull-down assay moderately interacts with CD4 in the ELISA assay. Functionally, we showed that AaVA-1 and NeST1 proteins promoted activation of CD4+ T cells. We propose the possible impact of these interactions and effects on mosquito-borne viral infections such as dengue, Zika, and chikungunya viruses. Overall, this study provides key insight into the vector-host (protein-protein) interaction network and suggests roles for these interactions in mosquito-borne viral infections.
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Aedes , Proteínas e Peptídeos Salivares , Alérgenos , Animais , Apirase , Humanos , Molécula 3 de Adesão Intercelular/metabolismo , Mosquitos Vetores , Proteínas Recombinantes/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
Interleukin-1α (IL-1α) plays an important role in inflammation and hematopoiesis. Many tumors have increased IL-1α expression. However, the immune regulatory role of secreted IL-1α in tumor development and whether it can be targeted for cancer therapy are still unclear. Here, we found that tumoral-secreted IL-1α significantly promoted hepatocellular carcinoma (HCC) development in vivo. Tumoral-released IL-1α were found to inhibit T and NK cell activation, and the killing capacity of CD8+ T cells. Moreover, MDSCs were dramatically increased by tumoral-released IL-1α in both spleens and tumors. Indeed, higher tumoral IL-1α expression is associated with increased tumoral infiltration of MDSCs in HCC patients. Further studies showed that tumoral-released IL-1α promoted MDSC recruitment to the tumor microenvironment through a CXCR2-dependent mechanism. Depletion of MDSCs could diminish the tumor-promoting effect of tumoral-released IL-1α. On the contrary, systemic administration of recombinant IL-1α protein significantly inhibited tumor development by activating T cells. In fact, IL-1α protein could promote T cell activation and enhance the cytotoxicity of CD8+ T cells in vitro. Thus, our study demonstrated that tumoral-released IL-1α promoted tumor development through recruiting MDSCs to inhibit T cell activation, while systemic IL-1α directly promoted anti-tumor T cell responses. We further identified calpain 1 as the major intracellular protease mediating tumoral IL-1α secretion. Calpain 1 KO tumors had diminished IL-1α release and reduced tumor development. Thus, our findings provide new insights into the functions of secreted IL-1α in tumor immunity and its implications for immunotherapy.
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Calpaína , Carcinoma Hepatocelular , Interleucina-1alfa , Neoplasias Hepáticas , Linfócitos T CD8-Positivos/imunologia , Calpaína/imunologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Humanos , Interleucina-1alfa/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Microambiente TumoralRESUMO
γδT cells represent a small percentage of T cells in circulation but are found in large numbers in certain organs. They are considered to be innate immune cells that can exert cytotoxic functions on target cells without MHC restriction. Moreover, γδT cells contribute to adaptive immune response via regulating other immune cells. Under the influence of cytokines, γδT cells can be polarized to different subsets in the tumor microenvironment. In this review, we aimed to summarize the current understanding of antigen recognition by γδT cells, and the immune regulation mediated by γδT cells in the tumor microenvironment. More importantly, we depicted the polarization and plasticity of γδT cells in the presence of different cytokines and their combinations, which provided the basis for γδT cell-based cancer immunotherapy targeting cytokine signals.
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Neoplasias , Receptores de Antígenos de Linfócitos T gama-delta , Citocinas , Humanos , Imunoterapia , Neoplasias/terapia , Linfócitos T , Microambiente TumoralRESUMO
γδT cells recognize and exert cytotoxicity against tumor cells independently of MHC restriction and have antigen presentation and regulatory functions to promote adaptive immune responses. They are considered as potential immune cells for cellular immunotherapy in cancer patients. However, it is challenging to ex vivo expand human γδT cells that have superb effector functions and long-term survival for adoptive cancer therapy. We found that IL-12/18 combination could drastically promote IFN-γ secretion and cytotoxicity in human γδT cells. However, the enhanced activation of human γδT cells is accompanied by increased apoptosis and elevated expressions of co-inhibitory receptors under the stimulation of IL-12/18. We further demonstrated that IL-12/18 induced apoptosis of human γδT cells was in a phosphoantigen or IFN-γ-independent manner. Transcriptomic analysis suggested that IL-12/18-induced apoptosis of human γδT cells was mediated by the activation of JNK pathway. p-JNK inhibitor (SP-600125) treatment effectively revived human γδT cells from the apoptosis induced by IL-12/18 and maintained their enhanced IFN-γ production and cytotoxicity against tumor cells. Our results provide a novel and feasible strategy for ex vivo expansion of cytokine-activated human γδT cells, which could promote the efficacy of γδT cell adoptive immunotherapy in cancer patients.
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Neoplasias , Receptores de Antígenos de Linfócitos T gama-delta , Linfócitos T , Humanos , Apoptose , Imunoterapia Adotiva , Interleucina-12 , Interleucina-18 , Linfócitos T/imunologia , MAP Quinase Quinase 4/antagonistas & inibidoresRESUMO
Although large diameter vessels made of polyurethane materials have been widely used in clinical practice, the biocompatibility and long-term patency of small diameter artificial vessels have not been well addressed. Any technological innovation and advancement in small-diameter artificial blood vessels is of great interest to the biomedical field. Here a novel technique is used to produce artificial blood vessels with a caliber of less than 6â mm and a wall thickness of less than 0.5â mm by rotational exposure, and to form a bionic inner wall with a periodically micro-nano structure inside the tube by laser double-beam interference. The polyethylene glycol diacrylate used is a widely recognized versatile biomaterial with good hydrophilicity, biocompatibility and low cytotoxicity. The effect of the bionic structure on the growth of hepatocellular carcinoma cells and human umbilical vein endothelial cells was investigated, and it was demonstrated that the prepared vessels with the bionic structure could largely promote the endothelialization process of the cells inside them.
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Linfócitos T CD8-Positivos/imunologia , Interferon Tipo I/biossíntese , Manganês/farmacologia , Neoplasias/imunologia , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Hidrodinâmica , Camundongos , Neoplasias/patologiaRESUMO
IL-Y, a synthetic member of IL-12 cytokine family, was found to exert potent immunosuppressive effects by inhibiting the differentiation and activation of Th1 and Th17 cells. However, the role of IL-Y in the development of chronic graft-versus-host disease (cGVHD) remains unknown. Here, using murine models of scleroderma-like and lupus-like cGVHD, we examined the function of IL-Y in the pathogenesis of cGVHD by hydrodynamically injecting minicircle-IL-Y expressing plasmids (MC IL-Y). In contrast with the reported immune suppressive function of IL-Y, administration of MC IL-Y enhanced cGVHD severity reflected by deteriorated multi-organ pathologic damages. In lupus-like cGVHD model, urine protein and the serum anti-dsDNA antibody (IgG) were significantly upregulated by IL-Y treatment. Further study demonstrated that IL-Y impacts both donor T and B cell response. In T cells, IL-Y inhibited the generation of CD4+Foxp3+ regulator T (Treg) cells during the development of cGVHD. IL-Y may also increase the infiltration of pathogenic TNF-α producing CD4+ and CD8+ T cells through IL-27Rα in recipient spleens, as this effect was diminished in IL-27Rα deficient T cells. Moreover, IL-Y enhanced the differentiation of ICOS+ T follicular helper (Tfh) cells. In B cells, the percentage of germinal center (GC) B cells in recipient spleens was significantly upregulated by MC IL-Y plasmid administration. The levels of co-stimulatory molecules, MHC-II and CD86, on B cells were also enhanced by IL-Y expression. Taken together, our data indicated that IL-Y promoted the process of cGVHD by activating pathogenic T and B cells.