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BACKGROUND: The unfolded protein response (UPR) is associated with immune cells that regulate the biological behavior of tumors. This article aims to combine UPR-associated genes with immune cells to find a prognostic marker and to verify its connection to the UPR. METHODS: Univariate cox analysis was used to screen prognostically relevant UPRs and further screened for key UPRs among them by machine learning. ssGSEA was used to calculate immune cell abundance. Univariate cox analysis was used to screen for prognostically relevant immune cells. Multivariate cox analysis was used to calculate UPR_score and Tumor Immune Microenvironment score (TIME_score). WGCNA was used to screen UPR-Immune-related (UI-related) genes. Consensus clustering analysis was used to classify patients into molecular subtype. Based on the UI-related genes, we classified colon adenocarcinoma (COAD) samples by cluster analysis. Single-cell analysis was used to analyze the role of UI-related genes. We detected the function of TIMP1 by cell counting and transwell. Immunoblotting was used to detect whether TIMP1 was regulated by key UPR genes. RESULTS: Combined UPR-related genes and immune cells can determine the prognosis of COAD patients. Cluster analysis showed that UI-related genes were associated with clinical features of COAD. Single-cell analysis revealed that UI-related genes may act through stromal cells. We defined three key UI-related genes by machine learning algorithms. Finally, we found that TIMP1, regulated by key genes of UPR, promoted colon cancer proliferation and metastasis. CONCLUSIONS: We found that TIMP1 was a prognostic marker and experimentally confirmed that TIMP1 was regulated by key genes of UPR.
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Biomarcadores de Tumor , Neoplasias del Colon , Inhibidor Tisular de Metaloproteinasa-1 , Microambiente Tumoral , Respuesta de Proteína Desplegada , Humanos , Respuesta de Proteína Desplegada/genética , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias del Colon/inmunología , Neoplasias del Colon/metabolismo , Neoplasias del Colon/mortalidad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Regulación Neoplásica de la Expresión Génica , Análisis por Conglomerados , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/inmunología , Adenocarcinoma/metabolismo , Aprendizaje Automático , Análisis de la Célula Individual/métodos , Femenino , Línea Celular Tumoral , MasculinoRESUMEN
Background: Chromatin regulators (CRs) are implicated in the development of cancer, but a comprehensive investigation of their role in colon adenocarcinoma (COAD) is inadequate. The purpose of this study is to find CRs that can provide recommendations for clinical diagnosis and treatment, and to explore the reasons why they serve as critical CRs. Methods: We obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted Gene Co-Expression Network Analysis (WGCNA) screened tumor-associated CRs. LASSO-Cox regression was used to construct the model and to screen key CRs together with support vector machine (SVM), the univariate Cox regression. We used single-cell data to explore the expression of CRs in cells and their communication. Immune infiltration, immune checkpoints, mutation, methylation, and drug sensitivity analyses were performed. Gene expression was verified by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Pan-cancer analysis was used to explore the importance of hub CRs. Results: We finally obtained 32 tumor-associated CRs. The prognostic model was constructed based on RCOR2, PPARGC1A, PKM, RAC3, PHF19, MYBBP1A, ORC1, and EYA2 by the LASSO-Cox regression. Single-cell data revealed that the model was immune-related. Combined with immune infiltration analysis, immune checkpoint analysis, and tumor immune dysfunction and exclusion (TIDE) analysis, the low-score risk group had more immune cell infiltration and better immune response. Mutation and methylation analysis showed that multiple CRs may be mutated and methylated in colon cancer. Drug sensitivity analysis revealed that the low-risk group may be more sensitive to several drugs and PKM was associated with multiple drugs. Combined with machine learning, PKM is perhaps the most critical gene in CRs. Pan-cancer analysis showed that PKM plays a role in the prognosis of cancers. Conclusions: We developed a prognostic model for COAD based on CRs. Increased expression of the core gene PKM is linked with a poor prognosis in several malignancies.
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Nitrogen application delays rice quality deterioration due to changes in its pasting characteristics; however, the underlying mechanisms remain unclear. Using a label-free quantitative proteomics approach, we identified differentially expressed proteins (DEPs) during storage in paddy rice treated with different nitrogen levels. On combining the changes in physiological indicators, high-nitrogen treatment was found to downregulate ß-1,3-glucanase, reduce the decomposition of cell wall components, downregulate three proteins involved in starch metabolism, decrease the range of the amylose content and increase the range of the amylopectin, upregulate three proteins related to the lysosomal pathway, and enhance glutelin degradation. In addition, it upregulated three proteins related to flavonoid synthesis, which enhanced the stress response ability of rice, thereby contributing to the stability of biological macromolecules. The discovery of these key DEPs provides potential targets for further control over the deterioration of crop seed storage quality.
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The nuclear resonant scattering (NRS) experiment requires photon-counting detectors with high time resolution, short dead time, large dynamic range, low noise, and large detection area. An 8-channel avalanche photodiode (APD) array detector system with high integrity, flexibility, and reliability has been developed to adapt to the demands of NRS experiments. The detector system mainly consists of four key parts: (i) an array-APD sensor, (ii) 8-channel integrated fast preamplifiers, (iii) the time-to-digital converter readout electronics, and (iv) a data acquisition system and EPICS support software. Remarkably, the system exhibits a time resolution of better than 500 ps and has a sufficiently low noise level, allowing for the lowest detection energy threshold of 4 keV. The performance of the new array-APD system as well as its real application in nuclear forward scattering (NFS) and nuclear resonant inelastic x-ray scattering (NRIXS) experiments was tested in two synchrotron facilities. With the new system, the NFS signal very close to the prompt electronic scattering signal can be extracted. Thanks to the customized EPICS-areaDetector-based control software, NRIXS spectra can be readily measured with time and energy information of the NRIXS signal stored in the raw data, which is promising for developing NRIXS data analysis in the time domain. The array-APD detector can be deployed for nuclear resonant scattering experiments at various synchrotron radiation facilities.
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tRNA-histidine guanyltransferase 1-like protein (THG1L), located in the mitochondria, plays a crucial role in the tRNA maturation process. Dysfunction of THG1L results in abnormal mitochondrial tRNA modification and neurodevelopmental disorders. To date, few studies have focused on THG1L-related cerebellar ataxia. Whole-exome sequencing revealed compound heterozygous variants NM_017872.5: [c.224A > G]; [c.369-8T > G] in THG1L in a 6-year-old boy with moderate cerebellar ataxia. The variant c.224A > G was demonstrated to downregulate its RNA and protein expression, and c.369-8 T > G resulted in a 7 bp insertion before exon 3. Our case expanded the gene variation and clinical spectrum of THG1L-related cerebellar ataxia.
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Ataxia Cerebelosa , Masculino , Humanos , Niño , Ataxia Cerebelosa/genética , Mutación , Imagen por Resonancia Magnética , Exones , ARN de Transferencia , LinajeRESUMEN
Colorectal cancer (CRC) is the third most common cancer in the world, and its incidence rate and mortality are on the rise in many countries. In recent years, with the improvement of economic conditions, people's living habits have changed, including lack of physical activity, poor diet patterns and circadian rhythm disorder. These risk factors can change the colon environment and the composition of intestinal microbiota. This state is called intestinal imbalance, which increases the risk of cancer. Probiotics, a class of microorganisms that help maintain gut microbial homeostasis and alleviate dysbiosis, may help prevent inflammation and colorectal cancer. These probiotics inhibit or ameliorate the effects of dysbiosis through the production of short-chain fatty acids (SCFAs), modulation of immunity, maintenance of the intestinal epithelial barrier, pro-apoptotic mechanisms, and other mechanisms. This review aims to explain the interaction between probiotics, the gut microenvironment and the gut microbiota, and summarize reports on the possibility of probiotics in the prevention and treatment of colorectal cancer.
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BACKGROUND: As an important regulatory mechanism to remove damaged mitochondria and maintain the balance between internal and external cells, mitochondrial autophagy plays a key role in the progression and treatment of cancer Onishi (EMBO J 40(3): e104705, 2021). The purpose of this study is to comprehensively analyze the role of mitochondrial autophagy-related genes in the progression of gastric cancer (GC) by RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq). METHODS: GSE26942, GSE54129,GSE66229,GSE183904 and other data sets were obtained by GEO databases. Using support vector machine recursive feature elimination (SVM-RVF) algorithm and random forest algorithm, the mitochondrial autophagy-related genes related to gastric cancer were obtained, respectively. After that, the model was constructed and the inflammatory factors, immune score and immune cell infiltration were analyzed. Furthermore, according to the scRNA-seq data of 28,836 cells from 13 GC samples, 18 cell clusters and 7 cell types were identified by scRNA-seq analysis. The expression level and signal pathway of related genes were verified by cell communication analysis. Finally, the regulatory network of cells was analyzed by SCENIC. RESULTS: MAP1LC3B, PGAW5, PINK1, TOMM40 and UBC are identified as key genes through machine learning algorithms. CXCL12-CXCR4, LGALS9-CD44, LGALS9-CD45 and MIF (CD74 + CD44) pathways may play an important role in endothelial cells with high score scores of T cells and monocytes in tumor environment. CEBPB, ETS1, GATA2, MATB, SPl1 and XBP1 were identified as candidate TF with specific regulatory expression in the GC cell cluster. CONCLUSION: The results of this study will provide implications for the study of the mechanism, diagnosis and treatment of mitochondrial autophagy in GC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Células Endoteliales , Mitocondrias/genética , Autofagia/genética , AlgoritmosRESUMEN
Cancer is a major cause of high morbidity and mortality worldwide. Several environmental, genetic and lifestyle factors are associated with the development of cancer in humans and result in suboptimal treatment. The human microbiota has been implicated in the pathophysiological process of cancer and has been used as a diagnostic, prognostic and risk assessment tool in cancer management. Notably, both extratumoural and intratumoural microbiota are important components of the tumor microenvironment, subtly influencing tumorigenesis, progression, treatment and prognosis. The potential oncogenic mechanisms of action of the intratumoural microbiota include induction of DNA damage, influence on cell signaling pathways and impairment of immune responses. Some naturally occurring or genetically engineered microorganisms can specifically accumulate and replicate in tumors and then initiate various anti-tumor programs, ultimately promoting the therapeutic effect of tumor microbiota and reducing the toxic and side effects of conventional tumor treatments, which may be conducive to the pursuit of accurate cancer treatment. In this review, we summarise evidence revealing the impact of the intratumoural microbiota on cancer occurrence and progress and potential therapeutic and diagnostic applications, which may be a promising novel strategy to inhibit tumor development and enhance therapeutic efficacy. Video Abstract.
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Carcinogénesis , Microbiota , Humanos , Transformación Celular Neoplásica , Daño del ADN , Microambiente TumoralRESUMEN
The nasal mucosa is the first barrier to pathogen invasion through the respiratory tract. Few studies have focused on nasal resistance to invasion by respiratory pathogens due to the lack of models related to the nasal mucosa. Hence, it is necessary to construct a nasal mucosal model to study host-pathogen interactions. We established a long-term in vitro sheep nasal mucosa explant model (NMEM), which exhibited typical epithelial cilia and epithelial proliferation ability within 11 days. Moreover, to evaluate whether the NMEM was suited for in vitro pathogenic study, we used pseudorabies virus (PRV) and showed that it successfully infected and produced severe lesions in the NMEM, particularly interferon (IFN)-stimulated gene product 15 (ISG15). IFN decreased significantly after the PRV infection. Similarly, we used this NMEM model to screen several antiviral substances, such as probiotics and drugs. A previous study showed that nasal commensal bacteria, particularly Bacillus subtilis, had high antiviral activity. Then, we used the NMEM to evaluate six sheep-derived B. subtilis strains and demonstrated that it significantly induced the production of IFN and expression of ISG15. The sheep-derived B. subtilis was pretreated with the sheep NMEM before the PRV infection to evaluate the antiviral effect. The results showed that NSV2 significantly inhibited infection by PRV and reduced the viral load (p < 0.05). Furthermore, NSV2 may inhibit PRV replication by enhancing ISGylation of cells. In conclusion, we established a reliable in vitro culture model of sheep NMEM, and applied it in antiviral research.
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Presenting with a poor prognosis, gastric cancer (GC) remains one of the leading causes of disease and death worldwide. Long non-coding RNAs (lncRNAs) regulate tumor formation and have been long used to predict tumor prognosis. N7-methylguanosine (m7G) is the most prevalent RNA modification. m7G-lncRNAs regulate GC onset and progression, but their precise mechanism in GC is unclear. The objective of this research was the development of a new m7G-related lncRNA signature as a biomarker for predicting GC survival rate and guiding treatment. The Cancer Genome Atlas database helped extract gene expression data and clinical information for GC. Pearson correlation analysis helped point out m7G-related lncRNAs. Univariate Cox analysis helped in identifying m7G-related lncRNA with predictive capability. The Lasso-Cox method helped point out seven lncRNAs for the purpose of establishing an m7G-related lncRNA prognostic signature (m7G-LPS), followed by the construction of a nomogram. Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, calibration plot of the nomogram model, receiver operating characteristic curve and principal component analysis were utilized for the verification of the risk model's reliability. Furthermore, q-PCR helped verify the lncRNAs expression of m7G-LPS in-vitro. The study subjects were classified into high and low-risk groups based on the median value of the risk score. Gene enrichment analysis confirmed the constructed m7G-LPS' correlation with RNA transcription and translation and multiple immune-related pathways. Analysis of the clinicopathological features revealed more progressive features in the high-risk group. CIBERSORT analysis showed the involvement of m7G-LPS in immune cell infiltration. The risk score was correlated with immune checkpoint gene expression, immune cell and immune function score, immune cell infiltration, and chemotherapy drug sensitivity. Therefore, our study shows that m7G-LPS constructed using seven m7G-related lncRNAs can predict the survival time of GC patients and guide chemotherapy and immunotherapy regimens as biomarker.
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ARN Largo no Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , ARN Largo no Codificante/genética , Lipopolisacáridos , Reproducibilidad de los Resultados , CalibraciónRESUMEN
Brown rice as a whole grain food is associated with various chronic diseases' reduced risks. In this study, the effects of different doses of nitrogen fertilization (0, 160, 210, 260, 315, and 420 kg N/ 100 m2) on bioactive compounds and antioxidant activity of brown rice (yanfeng47) were investigated. At nitrogen level of 210-260 kg N/100 m2, the content of TFC (302.65 mg/100 g), ß-sitosterol (1762.92 mg/100 g), stigmasterol (1358.735 mg/100 g), DPPH (74.57%), and OH free radical scavenging (74.19%) was the highest. The major phenolic acid was p-hydroxybenzoic acid. There were significant positive linear relationships between TFC (0.872, 0.843), ß-sitosterol (0.896, 0.657), stigmasterol (0.543, 0.771), p-hydroxybenzoic acid (0.871, 0.875), and DPPH, OH antioxidant activity. These indicated that TFC and phytosterols were the most important components in brown rice that had strong antioxidant activity. Composite score of principal components indicated 210 Kg N/100 m2 exhibited a more ideal dose of nitrogen for nutritional composition and antioxidant activity of brown rice.
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The mucosal barriers of a lamb's nasal cavity are composed of a multi-layer barrier designed to protect against the invasion of harmful microorganisms. However, despite the protective measures, respiratory pathogens still infect the sheep from the nasal cavity. Therefore, our study aimed to investigate the characteristics of lamb's nasal cavity barrier at different developmental stages. For nasal histological characteristics, our study revealed that the conchoidal curvature of the inferior nasal conch and the number of glands significantly increased with lamb development. For nasal mucosal barrier characteristics, physical and immune barriers were carefully explored. Initially, we observed that the thickness and proliferative capacity of nasal epithelial significantly increased from fetal to 21 days, which then decreased at 60 days. Then, our study showed that the number of goblet cells (GCs) of 21 days old lamb was significantly higher than in other stages of development. Besides, we found that the number of nasal immune cells, such as dendritic cells, CD3+ T cells, IgA+ B cells, and nasal-associated lymphoid tissue (NALT), were all significantly increased not only from the proximal to distal side in the nasal cavity but also with their age. Totally, our study revealed various characteristics of the mucosal barriers of a lamb's nasal cavity, which provide a reference for explaining the susceptibility of respiratory tract infection in lambs.
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Ovinos , AnimalesRESUMEN
Japonica rice is produced mainly in northeast China, Japan, and the Korean Peninsula. Polyphenols and flavonoids are the main antioxidants in japonica rice. This study reported the polyphenol content and antioxidant activity of nine brown and white japonica rice cultivars. The total phenolic and flavonoid contents of brown rice were in the ranges of 241.98-296.76 GAE mg/100 g, and 225.30-276.80 RE mg/100 g, respectively. These values were significantly higher than that of white rice by 118.98-206.06% and 135.0-217%, respectively. The bound fraction from phenolics and flavonoids contributed 41.1-63.6% and 62.22-78.19% of the total phenolic and flavonoid content in brown rice, respectively, while these ranges were 55.5-73.5% and 46.07-66.83% in white rice, respectively. p-Hydroxybenzonic acid was the predominant phenolic acid in japonica rice. All four antioxidant capacities of brown rice (DPPH, ABTS, OH, FRAP) were higher by up to 1.68-2.85 times than those of white rice. The PZ21 (Yanfeng 47) japonica rice variety has outstanding antioxidant capacity based on the weights of each antioxidant index. According to the differences of functional substances among varieties, it can provide guidance for consumers and theoretical basis for the production of healthy food.
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Nitrogen is a necessary element for plant growth; therefore, it is important to study the influence of N fertilisers on crop metabolites. In this study, we investigate the variability of endogenous metabolites in brown rice fertilised with different amounts of nitrogen. We identified 489 metabolites in brown rice. Compared to non-nitrogen fertilised groups, there were 59 differentially activated metabolic pathways in the nitrogen-fertilised groups. Additionally, there were significantly differential secondary metabolites, especially flavonoids, between groups treated with moderate (210 kg N/hm2) and excessive amounts of nitrogen (420 kg N/hm2). Nitrogen fertilisation upregulated linoleic acid metabolism and most steroids, steroid derivatives, and flavonoid compounds, which have antioxidant activity. The DPPH, ABTS, and hydroxyl radical scavenging rates were higher in fertilised groups than in the non-fertilised group. These findings provide a theoretical basis to enhance the health benefits of brown rice by improving fertilisation.
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Huge strides have been made in the navigation of gastric cancer surgery thanks to the improvement of intraoperative techniques. For now, the use of indocyanine green (ICG) enhanced fluorescence imaging has received promising results in detecting sentinel lymph nodes (SLNs) and tracing lymphatic drainages, which make it applicable for limited and precise lymphadenectomy. Nevertheless, issues of the lack of specificity and unpredictable false-negative lymph nodes were encountered in gastric oncologic surgery practice using ICG-enhanced fluorescence imaging (ICG-FI), which restrict its application. Here, we reviewed the current application of ICG-FI and assessed potential approaches to improving ICG-FI.
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The discovery of immune checkpoint inhibitors (ICIs) has ushered a new era for immunotherapy against malignant tumors through the killing effects of cytotoxic T lymphocytes in the tumor microenvironment (TME), resulting in long-lasting tumor suppression and regression. Nevertheless, given that ICIs are highly dependent on T cells in the TME and that most tumors lack T-cell infiltration, promoting the conversion of such immunosuppressive "cold" tumors to "hot" tumors is currently a key challenge in tumor immunotherapy. Herein, we systematically outlined the mechanisms underlying the formation of the immunosuppressive TME in cold tumors, including the role of immunosuppressive cells, impaired antigen presentation, transforming growth factor-ß, STAT3 signaling, adenosine, and interferon-γ signaling. Moreover, therapeutic strategies for promoting cold tumors to hot tumors with adequate T-cell infiltration were also discussed. Finally, the prospects of therapeutic tools such as oncolytic viruses, nanoparticles, and photothermal therapy in restoring immune activity in cold tumors were thoroughly reviewed.
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Crossing the endothelium from the entry site and spreading in the bloodstream are crucial but obscure steps in the pathogenesis of many emerging viruses. Previous studies confirmed that porcine epidemic diarrhea virus (PEDV) caused intestinal infection by intranasal inoculation. However, the role of the nasal endothelial barrier in PEDV translocation remains unclear. Here, we demonstrated that PEDV infection causes nasal endothelial dysfunction to favor viral dissemination. Intranasal inoculation with PEDV compromised the integrity of endothelial cells (ECs) in nasal microvessels. The matrix metalloproteinase 7 (MMP-7) released from the PEDV-infected nasal epithelial cells (NECs) contributed to the destruction of endothelial integrity by degrading the tight junctions, rather than direct PEDV infection. Moreover, the proinflammatory cytokines released from PEDV-infected NECs activated ECs to upregulate ICAM-1 expression, which favored peripheral blood mononuclear cells (PBMCs) migration. PEDV could further exploit migrated cells to favor viral dissemination. Together, our results reveal the mechanism by which PEDV manipulates the endothelial dysfunction to favor viral dissemination and provide novel insights into how coronavirus interacts with the endothelium. IMPORTANCE The endothelial barrier is the last but vital defense against systemic viral transmission. Porcine epidemic diarrhea virus (PEDV) can cause severe atrophic enteritis and acute viremia. However, the mechanisms by which the virus crosses the endothelial barrier and causes viremia are poorly understood. In this study, we revealed the mechanisms of endothelial dysfunction in PEDV infection. The viral infection activates NECs and causes the upregulation of MMP-7 and proinflammatory cytokines. Using NECs, ECs, and PBMCs as in vitro models, we determined that the released MMP-7 contributed to the destruction of endothelial barrier, and the released proinflammatory cytokines activated ECs to facilitate PBMCs migration. Moreover, the virus further exploited the migrated cells to promote viral dissemination. Thus, our results provide new insights into the mechanisms underlying endothelial dysfunction induced by coronavirus infection.
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Infecciones por Coronavirus , Endotelio , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Esparcimiento de Virus , Animales , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Citocinas , Endotelio/virología , Molécula 1 de Adhesión Intercelular/genética , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Metaloproteinasa 7 de la Matriz/metabolismo , Virus de la Diarrea Epidémica Porcina/fisiología , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/transmisión , Enfermedades de los Porcinos/virología , ViremiaRESUMEN
The location of intraepithelial lymphocytes (IELs) between epithelial cells provide a first line of immune defense against enteric infection. It is assumed that IELs migrate only along the basement membrane or into the lateral intercellular space (LIS) between epithelial cells. Here, we identify a unique transepithelial migration of porcine IELs as they move to the free surface of the intestinal epithelia. The major causative agent of neonatal diarrhea in piglets, porcine epidemic diarrhea virus (PEDV), increases the number of IELs entering the LIS and free surface of the intestinal epithelia, driven by chemokine CCL2 secreted from virus-infected intestinal epithelial cells. Remarkably, only virus pre-activated IELs inhibits PEDV infection and their antiviral activity depends on the further activation by virus-infected cells. Although high levels of perforin is detected in the co-culture system, the antiviral function of activated IELs is mainly mediated by IFN-γ secretion inducing robust antiviral response in virus-infected cells. Our results uncover a unique migratory behavior of porcine IELs as well as their protective role in the defense against intestinal infection.
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Infecciones por Coronavirus , Enfermedades Intestinales , Linfocitos Intraepiteliales , Virus de la Diarrea Epidémica Porcina , Virosis , Animales , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Virus de la Diarrea Epidémica Porcina/fisiología , PorcinosRESUMEN
Ammonia-N accumulation in the rice-crab co-culture system may have negative effects on the health of juvenile Eriocheir sinensis. In this study, physiological, transcriptomic, and metabolomic analyses were performed to explore the toxic responses in the hepatopancreas of juvenile E. sinensis exposed to 0, 0.75, and 2.99 mmol/L total ammonia-N for 24 h. We observed that the content of most amino acids and glycogen was significantly decreased after ammonia exposure. Acid phosphatase and alkaline phosphatase activities showed marginally increased trends after low ammonia exposure. Transcriptomic analysis indicated that immune defense, detoxification, and metabolic pathways were altered. Metabolomic analysis revealed that ammonia exposure affected energy metabolism and nucleotide metabolism. The combination of transcriptomic and metabolomic analyses revealed that the tricarboxylic acid cycle and amino acid consumption were enhanced for additional energy supply to cope with ammonia stress. Ammonia stress activated the immune defense system in juvenile E. sinensis. Moreover, the upregulation of detoxification genes and the acceleration of glycogen degradation for glucose supply are important adaptive mechanisms in response to high ammonia stress. Notably, ammonia stress may affect the nervous system of juvenile E. sinensis. Thus, our data provide a better understanding of the defensive mechanisms of E. sinensis against ammonia toxicity.
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Braquiuros , Contaminantes Químicos del Agua , Amoníaco/toxicidad , Animales , Braquiuros/genética , Hepatopáncreas , Transcriptoma , Contaminantes Químicos del Agua/toxicidadRESUMEN
Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. Owing to the lack of effective vaccines and specific therapeutic options for PEDV, it is pertinent to develop new and available antivirals. This study identified, for the first time, a salinomycin that actively inhibited PEDV replication in Vero cells in a dose-dependent manner. Furthermore, salinomycin significantly inhibited PEDV infection by suppressing the entry and post-entry of PEDV in Vero cells. It did not directly interact with or inactivate PEDV particles, but it significantly ameliorated the activation of Erk1/2, JNK and p38MAPK signaling pathways that are associated with PEDV infection. This implied that salinomycin inhibits PEDV replication by altering MAPK pathway activation. Notably, the PEDV induced increase in reactive oxidative species (ROS) was not decreased, indicating that salinomycin suppresses PEDV replication through a pathway that is an independent pathway of viral-induced ROS. Therefore, salinomycin is a potential drug that can be used for treating PEDV infection.