RESUMEN
Antibody-mediated rejection (AMR) can cause graft failure following renal transplantation. Neutrophils play a key role in AMR progression, but the exact mechanism remains unclear. We investigated the effect of neutrophils on AMR in a mouse kidney transplantation model. The mice were divided into five groups: syngeneic transplantation (Syn), allograft transplantation (Allo), and three differently treated AMR groups. The AMR mouse model was established using skin grafts to pre-sensitize recipient mice. Based on the AMR model, Ly6G-specific monoclonal antibodies were administered to deplete neutrophils (NEUT-/- + AMR) and TACI-Fc was used to block B-cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) signaling (TACI-Fcâ +â AMR). Pathological changes were assessed using hematoxylin-eosin and immunohistochemical staining. Banff values were evaluated using the Banff 2015 criteria. Donor-specific antibody (DSA) levels were assessed using flow cytometry, and BAFF and APRIL concentrations were measured using ELISA. Compared to the Syn and Allo groups, a significantly increased number of neutrophils and increased C4d and IgG deposition were observed in AMR mice, accompanied by elevated DSA levels. Neutrophil depletion inhibited inflammatory cell infiltration and reduced C4d and IgG deposition. Neutrophil depletion significantly decreased DSA levels after transplantation and suppressed BAFF and APRIL concentrations, suggesting a mechanism for attenuating AMR-induced graft damage. Similar results were obtained after blockading BAFF/APRIL using a TACI-Fc fusion protein. In summary, neutrophil infiltration increased in the AMR mouse renal transplantation model. Neutrophil depletion or blockading the BAFF/APRIL signaling pathway significantly alleviated AMR and may provide better options for the clinical treatment of AMR.
RESUMEN
Exposure to lipopolysaccharide (LPS) can lead to inflammation in a variety of tissues and organs. Selenium (Se) plays a crucial role in mitigating inflammatory damage. Compared with inorganic selenium, organic selenium, such as selenomethionine (SeMet), has the advantages of a higher absorption rate and lower toxicity in animals. This study examined the protective effects of SeMet on eggshell gland tissue damage caused by LPS. Hy-Line Brown laying hens were chosen as the experimental animals and were randomly assigned to four groups: control group (C), lipopolysaccharide group (LPS), SeMet group (Se), and SeMet + lipopolysaccharide group (Se + LPS). H&E staining and transmission electron microscope were performed to observe the pathological changes of eggshell glands, oxidative stress related indicators were measured using relevant kits, qRTâPCR and western blotting were used to evaluate the mRNA and protein levels of the Nrf2 pathway, necroptosis, and inflammation related indicators. The results showed that LPS treatment increased the content of malondialdehyde (MDA), decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and decreased the content of glutathione (GSH). LPS increased the levels of Keap1, RIPK1, RIPK3, MLKL, TNF-α, COX-2, and NF-κB, while decreasing the levels of HO-1, NQO1, Nrf2, and Caspase-8. However, SeMet treatment effectively reversed the changes of the above indicators, indicating that SeMet alleviates eggshell gland cell necroptosis-mediated inflammation induced by LPS via regulating the Keap1/Nrf2/HO-1 pathway. This study elucidated the mechanism by which SeMet alleviates LPS-induced eggshell gland tissue damage in Hy-Line Brown laying hens and provided a new direction for expanding the application of SeMet in the feeding and production of laying hens.
Asunto(s)
Selenio , Selenometionina , Femenino , Animales , Selenometionina/farmacología , Selenometionina/metabolismo , Lipopolisacáridos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Pollos/metabolismo , Selenio/farmacología , Selenio/metabolismo , Cáscara de Huevo/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Necroptosis , Inflamación/metabolismo , Estrés Oxidativo , Glutatión/metabolismo , Antioxidantes/farmacologíaRESUMEN
BACKGROUND: B-box (BBX) proteins play important roles in regulating plant growth, development, and abiotic stress responses. BBX family genes have been identified and functionally characterized in many plant species, but little is known about the BBX family in blueberry (Vaccinium corymbosum). RESULT: In this study, we identified 23 VcBBX genes from the Genome Database for Vaccinium (GDV). These VcBBXs can be divided into five clades based on gene structures and conserved domains in their encoded proteins. The prediction of cis-acting elements in the upstream sequences of VcBBX genes and protein-protein interactions indicated that VcBBX proteins are likely involved in phytohormone signaling pathways and abiotic stress responses. Analysis of transcriptome deep sequencing (RNA-seq) data showed that VcBBX genes exhibited organ-specific expression pattern and 11 VcBBX genes respond to ultraviolet B (UV-B) radiation. The co-expression analysis revealed that the encoded 11 VcBBX proteins act as bridges integrating UV-B and phytohormone signaling pathways in blueberry under UV-B radiation. Reverse-transcription quantitative PCR (RT-qPCR) analysis showed that most VcBBX genes respond to drought, salt, and cold stress. Among VcBBX proteins, VcBBX24 is highly expressed in all the organs, not only responds to abiotic stress, but it also interacts with proteins in UV-B and phytohormone signaling pathways, as revealed by computational analysis and co-expression analysis, and might be an important regulator integrating abiotic stress and phytohormone signaling networks. CONCLUSIONS: Twenty-three VcBBX genes were identified in blueberry, in which, 11 VcBBX genes respond to UV-B radiation, and act as bridges integrating UV-B and phytohormone signaling pathways according to RNA-seq data. The expression patterns under abiotic stress suggested that the functional roles of most VcBBX genes respose to drought, salt, and cold stress. Our study provides a useful reference for functional analysis of VcBBX genes and for improving abiotic stress tolerance in blueberry.
Asunto(s)
Arándanos Azules (Planta) , Arándanos Azules (Planta)/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Estrés Fisiológico/genética , Genoma de Planta , Transcriptoma , Respuesta al Choque por Frío , Proteínas de Plantas/metabolismo , Filogenia , Regulación de la Expresión Génica de las PlantasRESUMEN
Di (2-ethylhexyl) phthalate (DEHP) is a neuroendocrine disruptor that can cause multi-tissue organ damage by inducing oxidative stress. Evodiamine (EVO) is an indole alkaloid with anti-inflammatory, antitumor, and antioxidant pharmacological activity. In this manuscript, the effects of DEHP and EVO on the pyroptosis, necroptosis and immunology of grass carp hepatocytes (L8824) were investigated using DCFH-DA staining, PI staining, IF staining, AO/EB staining, LDH kit, qRT-PCR and protein Western blot. The results showed that DEHP exposure upregulated reactive oxygen species (ROS) levels, promoted the expression of TLR4/MyD88/NF-κB pathway, increased the expression of genes involved in cell pyroptosis pathway (LDH, NLRP3, ASC, caspase1, IL-1ß, IL-18 and GSDMD) and necroptosis-related genes (RIPK1, RIPK3 and MLKL). The expression of DEHP can also affect immune function, which can be demonstrated by variationsin the activation of antimicrobial peptides (LEAP2, HEPC, and ß-defensin) and inflammatory cytokines (TNF-α, IL-2, IL-6 and IL-10). EVO regulates cellular antioxidant capacity by inhibiting ROS burst, reduces DEHP-induced cell pyroptosis and necroptosis to some extent, and restores cellular immune function, after co-exposure with EVO. The TLR4 pathway was inhibited by the co-treatment of TLR4 inhibitor TLR-IN-C34 and DEHP, which attenuated the expression of cell pyroptosis, necroptosis, and immunosuppression. Thus, DEHP induced pyroptosis, necroptosis and abnormal immune function in L8824 cells by activating TLR4/MyD88/NF-κB pathway. In addition, EVO has a therapeutic effect on DEHP-induced toxic injury. This study further provides a theoretical basis for the risk assessment of plasticizer DEHP on aquatic organisms.
Asunto(s)
Carpas , Dietilhexil Ftalato , Animales , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Piroptosis/fisiología , Dietilhexil Ftalato/toxicidad , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 4/genética , Antioxidantes/farmacología , Carpas/metabolismo , Necroptosis , Hepatocitos/metabolismo , Terapia de InmunosupresiónRESUMEN
Pesticide mixtures can reduce pest resistance, however, their overuse severely threatens aquatic animal survival and public health. Avermectin (AVM) and imidacloprid (IMI) are potent insecticides often employed in agriculture. By inducing oxidative stress, these chemicals can induce cell death. Here, we evaluated the combined toxicity of AVM and IMI on EPC cells based on the concept of toxicity units (TU). We established EPC cell models exposed to AVM and IMI alone and in combination. The results showed that AVM and IMI had additive effects on the toxicity of EPC cells. Meanwhile, the co-exposure of AVM and IMI exacerbated oxidative stress and induced excessive production of reactive oxygen species (ROS), triggered Keap1/Nrf2/TXNIP axis, caused DNA damage and increased the expression of genes related to pyroptosis. In addition, co-exposure to AVM and IMI caused immunosuppression of EPC cells. The ROS inhibitor N-Acetyl-l-cysteine (NAC) can dramatically reverse these alterations brought on by AVM and IMI co-exposure. The findings above conclude that co-exposure to AVM and IMI causes DNA damage, pyroptosis, and immunosuppression in EPC cells through the ROS-mediated Keap1/Nrf2/TXNIP pathway. This study revealed the joint toxicity of AVM and IMI on EPC cells, and reminded people to consider its impact on aquatic animals when using pesticide mixtures.
Asunto(s)
Carcinoma , Plaguicidas , Animales , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Piroptosis , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Estrés Oxidativo , Plaguicidas/toxicidad , Daño del ADNRESUMEN
Tetrabromobisphenol A (TBBPA) is a common environmental pollutant which has multi-organ toxicity to mammals. Eucalyptol (EUC) has super antioxidant biological activity. However, in this experimental study, we probed into the mechanism of toxic of TBBPA exposure on Grass carp hepatocytes (L8824 cells) and the antagonistic impact of EUC on TBBPA. We treated L8824 cells with 8 µg/ml TBBPA and/or 20 µM EUC for 24 h in this test research. The experiment results suggested that TBBPA exposure induced elevated levels of reactive oxygen species (ROS), led to oxidative stress, decreased SOD and CAT activities, decreased GSH and T-AOC contents, exacerbated MDA accumulation, activated ASK1/JNK signaling pathway, and further increased the contents of mitochondrial dependent apoptosis pathway related indicators (Cyt-C, Bax, Caspase 9, Caspase 3), while Bcl-2 expression decreased. In addition, TBBPA exposure induced increased expression of TNF-α, IL-6, IL-1ß, and decreased expression of IL-2, IFN-γ, Hepcidin, ß-defensin, LEAP2. The oxidative stress level, ASK1/JNK signal pathway expression level, apoptosis ratio and cellular immune function of cells exposed to EUC alone did not change significantly. Combined exposure of TBBPA and EUC significantly reduced the proportion of apoptosis and restored cellular immune function. Therefore, these results suggest that EUC can effectively antagonize TBBPA-induced apoptosis and immune dysfunction of L8824 cells by regulating ROS/ASK1/JNK signaling pathway.
Asunto(s)
Carpas , Sistema de Señalización de MAP Quinasas , Animales , Especies Reactivas de Oxígeno/metabolismo , Eucaliptol/farmacología , Carpas/metabolismo , Hepatocitos/metabolismo , Apoptosis , Mamíferos/metabolismoRESUMEN
In this work, we report a novel and ultrasensitive dual-signal fluorescence emission detection system for protamine and trypsin based on the electrostatic interaction between polyethyleneimine (PEI) surface-modified positively charged carbon quantum dots (CDs-PEI) and the anionic fluorescent dye Eosin Y. The fluorescence system exhibited yellow-green fluorescence from Eosin Y and blue fluorescence from CDs-PEI. As a cationic peptide, protamine quenched the yellow-green fluorescence of Eosin Y at 542 nm through electrostatic interaction. In the presence of trypsin, protamine was specifically hydrolyzed by trypsin, which led to the subsequent recovery of the fluorescence of Eosin Y. Simultaneously, the blue fluorescence emission of CDs-PEI at 452 nm remained constant during the whole process. Hence, a ratiometric fluorescent nanoprobe for protamine and trypsin detection with high sensitivity was successfully constructed based on CDs-PEI and Eosin Y. For protamine detection, the ratiometric fluorescence intensity (I542/I452) exhibited an excellent linear relationship in the range of 0.1-5.2 µg mL-1 with a limit of detection (LOD) of 0.03 µg mL-1. And the linear relationship between I542/I452 and trypsin concentration ranged from 0.4 to 56 ng mL-1 with an LOD of 0.21 ng mL-1. Upon evaluating the performance of this method for the detection of trypsin in actual human urine samples, satisfactory results were finally obtained.
Asunto(s)
Polietileneimina , Puntos Cuánticos , Carbono , Eosina Amarillenta-(YS) , Colorantes Fluorescentes , Humanos , Límite de Detección , Protaminas , Espectrometría de Fluorescencia , TripsinaRESUMEN
Atrazine (ATR) is a commonly used triazine herbicide, which will remain in the water source, soil and biological muscle tissue for a long time, threatening the survival of related organisms and future generations. Tannic acid (TAN), a glucosyl compound found in gallnuts, has previously been shown to antagonize heavy metal toxicity, antioxidant activity, and inflammation. However, it is unclear whether TAN can antagonize ATR-induced Grass carp hepatocytes (L8824 cells) cytotoxicity. Therefore, we treated L8824 cells with 3 µg mL-1 ATR for 24 h to establish a toxic group model. The experimental data of flow cytometry and AO/EB staining together showed that the ratio of apoptosis and necrosis in L8824 cells after ATR exposure was significantly higher than that in the control group. Furthermore, RT-qPCR showed that inflammatory factors (TNF-α, IL-1ß, IL-6, INF-γ) were up-regulated and antimicrobial peptides (hepcidin, ß-defensin and LEAP2) were induced down-regulated in L8824 cells, leading to immune dysfunction. The measurement results of oxidative stress-related indicators showed that the levels of ROS and MDA increased after ATR exposure, the overall anti-oxidative system was down-regulated. Western blotting confirmed that TNF-α/TNFR 1-related genes were also up-regulated. This indicates that ATR stimulates oxidative stress in L8824 cells, which in turn promotes the binding of TNF-α to TNFR 1. In addition, TRADD, FADD, Caspase-3, P53, RIP1, RIP3 and MLKL were found to be significantly up-regulated by Western blotting and RT-qPCR. Conditioned after ATR exposure compared to controls. It indicates that ATR activates apoptosis and necrosis of TNF-α/TNFR 1 pathway by inducing oxidative stress in L8824 cells. Furthermore, the use of TAN (5 µM) significantly alleviated the toxic effects of ATR on L8824 cells mentioned above. In conclusion, TAN restrains ATR-induced apoptosis, programmed necrosis and immune dysfunction through the ROS/TNF-α/TNFR 1 pathway.
Asunto(s)
Atrazina , Carpas , Animales , Apoptosis , Atrazina/toxicidad , Carpas/metabolismo , Hepatocitos/metabolismo , Necrosis , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Diisobutyl phthalate (DiBP), one of the commonly used plasticizers in industry, is an endocrine disruptor and environmental contaminant that can persist in water and threaten the health of aquatic creatures. Eucalyptol (Euc), a monoterpenoid extracted from plants, has been proved to have anti-inflammatory, antioxidant, and detoxification properties. However, the protective mechanism of Euc against cell injury caused by DiBP exposure and the involvement of apoptosis, autophagy, and immunity remains unknown. In the current investigation, 27.8 µg/mL DiBP or/and 20 µM Euc has been applied to Ctenopharyngodon idellus kidney (CIK) cells for 24 h. The findings showed that exposure to DiBP raised intracellular ROS levels, inducing oxidative stress, and enhanced the rate of apoptosis as well as the expression of the apoptotic markers Bax, Caspase3, Caspase9, and Cytc while decreasing the expression of Bcl-2. Furthermore, DiBP inhibited IL-2, IFN-γ, Hepcidin-1, and ß-defensin expression and elevated TNF-α, and IL-1ß levels, causing immune dysfunction. DiBP and Euc co-treatment significantly activated the Keap1/Nrf2/HO-1 pathway, restored antioxidant enzyme activity, and elevated autophagy pathway-associated genes ATG5, Beclin1, and LC3B decreased p62 expression, enhanced cell autophagy, reduced apoptosis, and improved immunity. In conclusion, Euc promotes autophagy, alleviates DiBP-induced apoptosis, and improves immunological dysfunction in CIK cells by regulating the Keap1/Nrf2/HO-1 pathway. These results demonstrated the threat of DiBP exposure to fish while providing a theoretical foundation for using Euc in aquaculture.
Asunto(s)
Carpas , Disruptores Endocrinos , beta-Defensinas , Animales , Antioxidantes/farmacología , Apoptosis , Autofagia , Beclina-1 , Carpas/metabolismo , Dibutil Ftalato/análogos & derivados , Eucaliptol/farmacología , Hepcidinas/metabolismo , Interleucina-2 , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Riñón/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Plastificantes , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Agua , Proteína X Asociada a bcl-2/metabolismo , beta-Defensinas/metabolismoRESUMEN
A Co, N co-doped porous carbon-based nanozyme (Co-N-C nanozyme) has been fabricated. Taking advantages of the excellent oxidase catalytic activity and significant stability of Co-N-C nanozyme, we propose a fluorescence and colorimetric system based on Co-N-C nanozyme and red-emitting carbon quantum dots (RCDs) for butyrylcholinesterase (BChE) sensing. As the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) was catalyzed and oxidized by Co-N-C nanozyme, the generated oxTMB had a new absorption peak at 652 nm, which resulted in the significant quenching of the fluorescence of the carbon quantum dots at 610 nm. Under the catalysis of BChE, thiocholine was generated from the hydrolysis of S-butyrylthiocholine iodide (BTCh), and the as-generated thiocholine effectively inhibited the oxidation of TMB catalyzed by Co-N-C nanozyme, leading to a decrease of the absorption of oxTMB at 652 nm and effective fluorescence recovery of RCDs. By measuring the absorbance of produced oxTMB at 652 nm and the fluorescence of RCDs at 610 nm, the fluorescence and colorimetric system both exhibited an outstanding linear response to the activity of BChE in the range 0.5 to 40 U L-1, with a detection limit of 0.16 U L-1 and 0.21 U L-1, respectively. Furthermore, this established dual-channel biosensing strategy has been successfully applied to the determination of BChE in human serum samples. The present work has effectively expanded the development and application of nanozyme in biosensing.
Asunto(s)
Técnicas Biosensibles , Butirilcolinesterasa , Colorimetría , Técnicas Biosensibles/métodos , Butirilcolinesterasa/análisis , Butirilcolinesterasa/química , Carbono , Colorimetría/métodos , Humanos , Nanoestructuras/química , Oxidorreductasas , Porosidad , TiocolinaRESUMEN
The direct oncolytic effect of Newcastle disease virus (NDV) depends on the following two aspects: the susceptibility of cancer cells to virus infection and the ability of virus itself to lyse cancer cells. First, we investigate the susceptibility of cancer cells to NDV infection, HepG2, MDA-MB-231, and SH-SY5Y cells were susceptible, A549, MCF7, and LoVo cells were less susceptible. To investigate the molecular mechanism responsible for cancer cell susceptibility, transcriptome sequencing was carried out. We found that the levels of alpha-sialic acid acyltransferase were upregulated in MDA-MB-231 cells compared with MCF7 cells, and the interferon was downregulated. Second, to optimize the oncolytic capacity of the wild-type rClone30, a series of chimeric viruses rClone30-Anh(HN), rClone30-Anh(F), and rClone30-Anh(HN-F) were constructed by exchanging the HN gene, F gene or both of non-lytic rClone30 strain with lytic strain Anhinga. rClone30-Anh(F) and rClone30-Anh(HN-F) enhanced the oncolytic effect of the rClone30, and this enhancement is more obvious in the susceptible cells. The oncolytic mechanism of rClone30-Anh(F) was analyzed by transcriptome analyses, in comparison with rClone30, rClone30-Anh(F) upregulated the expression of ATG5, Beclin 1, and MAP1LC3B, thus activating autophagy and promoting the production of syncytia. In conclusion, our study provides a strategy to enhance the oncolytic effect of rClone30.
Asunto(s)
Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Animales , Línea Celular Tumoral , Virus de la Enfermedad de Newcastle/genética , Virus Oncolíticos/genética , Replicación ViralRESUMEN
Selenium (Se) is involved in many physiopathologic processes in humans and animals and is strongly associated with the development of heart disease. Lipopolysaccharides (LPS) are cell wall components of gram-negative bacteria that are present in large quantities during environmental pollution. To investigate the mechanism of LPS-induced cardiac injury and the efficacy of the therapeutic effect of SeMet on LPS, a chicken model supplemented with selenomethionine (SeMet) and/or LPS treatment, as well as a primary chicken embryo cardiomyocyte model with the combined effect of SeMet / JAK2 inhibitor (INCB018424) and/or LPS were established in this experiment. CCK8 kit, Trypan blue staining, DCFH-DA staining, oxidative stress kits, immunofluorescence staining, LDH kit, real-time fluorescence quantitative PCR, and western blot were used. The results proved that LPS exposure led to ROS explosion, hindered the antioxidant system, promoted the expression of the JAK2 pathway, and increased the expression of genes involved in the pyroptosis pathway, inflammatory factors, and heat shock proteins (HSPs). Upon co-treatment with SeMet and LPS, SeMet reduced LPS-induced pyroptosis and inflammation and restored the expression of HSPs by inhibiting the ROS burst and modulating the antioxidant capacity. Co-treatment with INCB018424 and LPS resulted in inhibited of the JAK2 pathway, attenuating pyroptosis, inflammation, and high expression of HSPs. Thus, LPS induced pyroptosis, inflammation, and changes in HSPs activity by activating of the JAK2 / STAT3 / A20 signaling axis in chicken hearts. Moreover, SeMet has a positive effect on LPS-induced injury. This work further provides a theoretical basis for treating cardiac injury by SeMet.
Asunto(s)
Antioxidantes , Nitrilos , Pirazoles , Pirimidinas , Selenometionina , Animales , Embrión de Pollo , Antioxidantes/metabolismo , Pollos/metabolismo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Janus Quinasa 2/metabolismo , Lipopolisacáridos/toxicidad , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Piroptosis , Especies Reactivas de Oxígeno/metabolismo , Selenometionina/farmacología , Selenometionina/análisis , Selenometionina/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
INTRODUCTION: Bisphenol A (BPA) is a widespread environmental pollutant which has serious toxic effects on organisms. One of the crucial trace elements is selenium (Se), whose shortage can harm biological tissues and enhance the toxicity of contaminants, in which apoptosis and autophagy are core events. OBJECTIVES: An in vivo model was established to investigate the effects of BPA and low-Se on chicken pancreatic tissue, and identify the possible potential molecular mechanism. METHODS: A total of 80 1-day-old broiler chickens (Xinghua Chicken Farm, Harbin, China) were stochastically divided into 4 groups (n = 20/group): Control group, BPA group, low-Se group, and low-Se + BPA group. Pancreatic tissue was collected at day 42 to detect changes in markers. RESULTS: First, the data showed that BPA and low-Se exposure gave rose to structural abnormalities in pancreatic tissue, oxidative stress, mitochondrial dysfunction and homeostasis imbalance, apoptosis and mitophagy. In addition, the co-exposure of BPA and low-Se caused the most serious damage to pancreatic tissue. In terms of mechanism, it was found that apoptosis and mitophagy induced by BPA and low-Se were related to the activation of PTEN/PI3K/AKT/mTOR pathway. CONCLUSION: In summary, the study found that BPA and low-Se exacerbated mitochondria damage, apoptosis and mitophagy by regulating the PTEN/PI3K/AKT/mTOR pathway.
RESUMEN
After polymer flooding, the heterogeneity between different layers intensifies, forming intricate seepage channels and fluid diversions, which results in decreased circulation efficiency and lower recovery rates, leaving a significant amount of residual oil trapped within the reservoir. Understanding the characteristics of residual oil occurrence is crucial for enhancing oil recovery post-polymer flooding. This study focused on sandstone reservoirs with varying permeability in the Saertu block of the Daqing oilfield. Using cryosectioning and laser scanning confocal microscopy, the occurrence characteristics of the residual oil in these sandstone reservoirs post-polymer flooding were investigated. Additionally, micro-CT and scanning electron microscopy were employed to analyze the impact of the pore structure on the distribution characteristics of the residual oil. The results indicate that laser scanning confocal images reveal that post-polymer flooding, the residual oil in high- and low-permeability sandstone reservoirs predominantly exists in a bound state (average > 47%), mostly as particle-adsorbed oil. In contrast, the residual oil in medium-permeability reservoirs is primarily in a free state (average > 49%), mostly as intergranular-adsorbed oil. In high-permeability sandstone reservoirs, heavy oil components are mainly in a particle-adsorbed form; in medium-permeability sandstone reservoirs, residual oil predominantly consists of heavy components, with most light components occurring in a clustered form; in low-permeability sandstone reservoirs, clustered residual oil exists in a balanced coexistence of light and heavy components, while the heavy components primarily exist in a particle-adsorbed form. Post-polymer flooding, the large pore-throat structure in high-permeability sandstone reservoirs results in effective displacement and less free residual oil; medium-permeability sandstone reservoirs, with medium-large pores and throats, have preferential channels and fine particles blocking the throats, leading to some unswept pores and more free residual oil; low-permeability sandstone reservoirs, with small pores and throats, exhibit weak displacement forces and poor mobility, resulting in more bound residual oil. The distribution and content of clay particles and clay minerals, along with the complex microscopic pore structure, are the main factors causing the differences in the residual oil occurrence states in sandstones with varying permeability.
RESUMEN
Infectious bursal disease (IBD) is a widespread problem in the poultry industry, and vaccination is the primary preventive method. However, moderately virulent vaccines may damage the bursa, necessitating the development of a safe and effective vaccine. The Newcastle disease virus (NDV) has been explored as a vector for vaccine development. In this study, reverse genetic technology was used to obtain three recombinant viruses, namely, rClone30-VP2L (P/M)-chGM-CSF (NP), rClone30-chGM-CSF (P/M)-VP2L (NP), and rClone30-VP2L-chGM-CSF (P/M). Animal experiments showed that the three biological adjuvant bivalent vaccines effectively increased anti-NDV and anti-infectious bursal disease virus (IBDV) titres, enhancing both humoral and cellular immune responses in chickens without leading to any harm. Amongst the three biological adjuvant bivalent vaccines, the rClone30-chGM-CSF (P/M)-VP2L (NP) group had higher levels of anti-NDV antibodies at 14 days after the first immunization and stimulated a greater humoral immune response in 7-10 days. While, the rClone30-VP2L (P/M)-chGM-CSF (NP) group was the most effective in producing a higher level of IBDV antibody response. In conclusion, these three vaccines can induce immune responses more rapidly and effectively, streamline production processes, be cost-effective, and provide a new avenue for the development of Newcastle disease (ND) and IBD bivalent vaccines.
Asunto(s)
Anticuerpos Antivirales , Infecciones por Birnaviridae , Pollos , Virus de la Enfermedad Infecciosa de la Bolsa , Enfermedad de Newcastle , Virus de la Enfermedad de Newcastle , Enfermedades de las Aves de Corral , Vacunas Virales , Animales , Vacunas Virales/inmunología , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/inmunología , Infecciones por Birnaviridae/prevención & control , Infecciones por Birnaviridae/inmunología , Infecciones por Birnaviridae/veterinaria , Virus de la Enfermedad de Newcastle/inmunología , Virus de la Enfermedad de Newcastle/genética , Virus de la Enfermedad Infecciosa de la Bolsa/inmunología , Virus de la Enfermedad Infecciosa de la Bolsa/genética , Enfermedad de Newcastle/prevención & control , Enfermedad de Newcastle/inmunología , Anticuerpos Antivirales/sangre , Inmunidad Humoral , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes de Vacunas , Inmunidad Celular , VacunaciónRESUMEN
The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.
Asunto(s)
Interleucinas , Virus de la Enfermedad de Newcastle , Viroterapia Oncolítica , Virus Oncolíticos , Animales , Virus de la Enfermedad de Newcastle/genética , Virus de la Enfermedad de Newcastle/fisiología , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genética , Virus Oncolíticos/fisiología , Humanos , Ratones , Línea Celular Tumoral , Interleucinas/genética , Interleucinas/metabolismo , Neoplasias Hepáticas/terapia , Ratones Endogámicos BALB C , Carcinoma Hepatocelular/terapia , Apoptosis , Neovascularización Patológica/terapia , Proliferación Celular , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Células Dendríticas/inmunología , Linfocitos T/inmunologíaRESUMEN
As an endocrine cytokine, fibroblast growth factor 21 (FGF21) exhibits anti-inflammatory properties. With the development of lupus nephritis (LN), which is tightly related to pathogenic factors, including inflammation and immune cell dysregulation, we explored the impact of Fibroblast Growth Factor 21 (FGF21) as well as its underlying mechanism. We induced an in vivo LN model using pristane in both wild-type C57BL/6 and FGF21 knockout (FGF21-/-) mice. LN serum obtained from 32-week-old wild-type LN mice was used to stimulate RAW264.7 and human renal tubular epithelial (HK-2) cells to mimic an in vitro LN model. Moreover, our findings revealed that FGF21-/- mice showed more severe kidney injury compared to wild-type mice, as evidenced by increased levels of renal function markers, inflammatory factors, and fibrosis markers. Notably, exogenous administration of FGF21 to wild-type LN mice markedly mitigated these adverse effects. Additionally, we used tandem mass tag (TMT)-based quantitative proteomics to detect differentially expressed proteins following FGF21 treatment. Results indicated that 121 differentially expressed proteins influenced by FGF21 were involved in biological processes such as immune response and complement activation. Significantly upregulated protein Irgm 1, coupled with modulated inflammatory response, appeared to contribute to the beneficial effects of FGF21. Furthermore, Western blot analysis demonstrated that FGF21 upregulated Irgm 1 while inhibiting nucleotide-binding oligomerization domain-like receptors family pyrin domain including 3 (NLRP3) inflammasome expression. Silencing Irgm 1, in turn, reversed FGF21's inhibitory effect on NLRP3 inflammasome. In summary, FGF21 can potentially alleviate pristane-induced lupus nephritis in mice, possibly through the FGF21/Irgm 1/NLRP3 inflammasome pathway.
Asunto(s)
Factores de Crecimiento de Fibroblastos , Inflamasomas , Nefritis Lúpica , Terpenos , Animales , Humanos , Ratones , Inflamasomas/metabolismo , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismoRESUMEN
Microparticles (MPs) are vesicles released from activated or apoptotic cells. MP derive from various cells, most notably platelets, but also leucocytes, lymphocytes, erythrocytes, and endothelial cells. The aim of this study was to investigate endothelial MP (EMP), platelet MP (PMP), lymphocyte MP and monocyte MP and TF-positive MPs (TF+ MPs) in patients with coronary heart disease (CHD), and to evaluate the correlation of these MPs with Interleukin-6 (IL-6) and C-reactive protein (CRP). Different cell-derived MPs and TF+ MPs were analyzed by flow cytometry in 40 patients with myocardial infarction (MI), 30 unstable angina (UA), 20 stable angina (SA) and 20 healthy individuals, and IL-6 and CRP were determined by ELISA and special protein analyzer, respectively. Compared with SA and control, EMP and PMP was significantly elevated in MI and UA (P < 0.001), and TF+ MPs was significantly elevated in MI and UA (P < 0.001). EMP and PMP correlated with IL-6 (r = 0.822, P < 0.001 and r = 0.567, P < 0.001; respectively) or CRP level (r = 0.597, P < 0.001 and r = 0.66, P < 0.001; respectively). Different cell-derived MPs in CHD may indicate the different pathophysiological changes in vessels, and MPs may both participate in the development of thrombosis and enhance the vascular inflammation.
Asunto(s)
Proteína C-Reactiva/metabolismo , Micropartículas Derivadas de Células/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Interleucina-6/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Humanos , Persona de Mediana EdadRESUMEN
Trimethyltin chloride (TMT) is an organotin-based contaminant present in the water environment that poses a great threat to aquatic organisms and humans. The liver is the detoxification organ of the body and TMT exposure accumulates in the liver. Tea polyphenol (TP) is a natural antioxidant extracted from tea leaves and has been widely used as a food and feed additive. To investigate the mechanism of toxicity caused by TMT exposure on grass carp hepatocytes (L8824 cells) and the mitigating effect of TP, we established a hepatocyte model of TMT toxicity and/or TP treatment. L8824 cells were treated with 0.5 µM of TMT and/or 4 µg/mL of TP for 24 h and assayed for relevant indices. The results showed that TMT exposure caused oxidative stress, resulting in increased intracellular ROS content, resulting in intracellular ROS accumulation and increased MDA content, and inhibiting the activities of T-AOC, SOD, CAT, and GSH. Meanwhile, TMT exposure activated the endoplasmic reticulum apoptotic signaling pathway, resulting in abnormal expression of GRP78, ATF-6, IRE1, PERK, Caspase-3 and Caspase-12. In addition, TMT exposure also led to up-regulation of cytokines IL-1ß, IL-6, TNF-α, and decreased expression of IL-2, IFN-γ, and antimicrobial peptides Hepcidin, ß-defensin, and LEAP2. However, the addition of TP could mitigate the above changes. In conclusion, TP can alleviate TMT exposure-mediated hepatotoxicity by inhibiting ROS/ER stress in L8824 cells. In addition, this trial enriches the cytotoxicity study of TMT and provides a new theoretical basis for the use of TP as a mitigating agent for TMT.