OTUD1 enhances gastric cancer aggressiveness by deubiquitinating EBV-encoded protein BALF1 to stabilize the apoptosis inhibitor Bcl-2.

The Epstein-Barr virus (EBV) is implicated in several cancers, including EBV-associated gastric cancer (EBVaGC). This study focuses on EBV-encoded BALF1 (BamH1 A fragment leftward reading frame 1), a key apoptosis regulator in EBV-related cancers, whose specific impact on EBVaGC was previously unknown. Our findings indicate that BALF1 overexpression in gastric cancer cells significantly enhances their proliferation, migration, and resistance to chemotherapy-induced apoptosis, confirming BALF1's oncogenic potential. A novel discovery is that BALF1 undergoes degradation via the ubiquitin-proteasome pathway. Through analysis of 69 deubiquitinating enzymes (DUBs), ovarian tumor protease (OTU) domain-containing protein 1 (OTUD1) emerged as a vital regulator for maintaining BALF1 protein stability. Furthermore, BALF1 was found to play a role in regulating the stability of the B-cell lymphoma-2 (Bcl-2) protein, increasing its levels through deubiquitination. This mechanism reveals BALF1's multifaceted oncogenic role in gastric cancer, as it contributes both directly and indirectly to cancer progression, particularly by stabilizing Bcl-2, known for its anti-apoptotic characteristics. These insights significantly deepen our understanding of EBV's involvement in the pathogenesis of gastric cancer. The elucidation of OTUD1's role in BALF1 regulation and its influence on Bcl-2 stabilization provide new avenues for therapeutic intervention in EBVaGC, bridging the gap between viral oncogenesis and cellular protein regulation and offering a more holistic view of gastric cancer development under the influence of EBV.

The preventive effects of Lactobacillus casei 03 on Escherichia coli-induced mastitis in vitro and in vivo.

BACKGROUND: Lactobacillus casei possesses many kinds of bioactivities, such as anti-inflammation and anti-oxidant, and has been applied to treating multiple inflammatory diseases. However, its role in mastitis prevention has remained ambiguous. METHODS: This study aimed to examine the mechanisms underlying the preventive effects of L. casei 03 against E. coli- mastitis utilizing bovine mammary epithelial cells (BMECs) and a mouse model. RESULTS: In vitro assays revealed pretreatment with L. casei 03 reduced the apoptotic ratio and the mRNA expression levels of IL1ß, IL6 and TNFα and suppressed phosphorylation of p65, IκBα, p38, JNK and ERK in the NF-κB signaling pathway and MAPK signaling pathway. Furthermore, in vivo tests indicated that intramammary infusion of L. casei 03 relieved pathological changes, reduced the secretion of IL1ß, IL6 and TNFα and MPO activity in the mouse mastitis model. CONCLUSIONS: These data suggest that L. casei 03 exerts protective effects against E. coli-induced mastitis in vitro and in vivo and may hold promise as a novel agent for the prevention and treatment of mastitis.

Characterization of the Roles of Suppressor of Cytokine Signaling-3 in Esophageal Carcinoma.

This study was aimed to analyze the diagnostic, therapeutic, and prognostic value of the suppressor of cytokine signaling 3 (SOCS3) in pancancer, especially in esophageal carcinoma (ESCA), and investigate the role of SOCS3 in the tumorigenesis and progression of ESCA. We used a variety of bioinformatics methods to explore the expression of SOCS3 in 33 kinds of cancers and evaluate its potential role in the pathogenesis, prognosis, immune microenvironment, immune evasion, and therapeutic response of cancers. The results indicated that SOCS3 was upregulated in 10 cancers, downregulated in 12 cancers, and upregulated in ESCA. Mutation and amplification were the main causes of abnormal expression of SOCS3 in pancancer. In ESCA, expression of SOCS3 was negatively correlated with methylation. The analysis showed that ESCA patients with low SOCS3 levels had better overall survival. Furthermore, the SOCS3 level was positively related to the ESTIMATE score, immune score, stromal score, and negatively related to tumor purity. In ESCA, a significant association was found between SOCS3 and several immune checkpoint genes. In addition, SOCS3 was associated with sensitivity to 59 drugs. Next, the role of SOCS3 in ESCA was investigated in ECA109, EC9706 cells, and in xenografted mouse model. SOCS3 was confirmed to be upregulated in ESCA cells. Knockdown of SOCS3 decreased the proliferation, migration, and invasion of ESCA cells while increasing apoptosis. Meanwhile, downregulation of SOCS3 activated the nuclear factor kappa-B signaling pathway and inhibited ESCA tumorigenesis in vivo. In conclusion, high SOCS3 expression is closely related to the occurrence and progression of ESCA and can be used as a therapeutic target and prognostic biomarker for ESCA.

The Prevention Effect of Lactobacillus plantarum 17-5 on Escherichia coli-Induced Mastitis in Mice.

Mastitis is the most economically important disease affecting the dairy industry worldwide. Lactobacillus plantarum, an important probiotic with a wide range of applications, has potential anti-inflammatory properties and has become a currently strong candidate for mastitis therapies. In the current study, we evaluated the prevention effect of Lactobacillus plantarum 17-5 on Escherichia coli-induced mastitis in mice. The results showed that pretreatment with L. plantarum 17-5 maintained the integrity of tight junctions; improved inflammatory injury; decreased MPO activity and the mRNA expression levels of IL1ß, IL6, and TNFα; and inhibited the NF-κB and MAPK signaling pathways in mice mammary tissue. The results indicated that Lactobacillus plantarum 17-5 had excellent anti-inflammatory activities and could be developed into microecological preparation for clinical use to prevent mastitis.

The pathogenic potential and genetic attributes of Escherichia coli in milk from dairy cows with subclinical mastitis.

The centrality of milk and dairy products to the human diet allows potential pathogens to pose a threat to human health. Pathogenic Escherichia coli is a zoonotic foodborne pathogen with many virulence genes which cause variations in its pathogenicity. The current study aimed to investigate the pathogenic potential of E. coli from milk of dairy cows with subclinical mastitis and evaluate the genetic relatedness to E. coli from human sources. The majority of the E. coli isolates belonged to the A (55.0%) and B2 (22.5%) phylogenetic groups and the most prevalent virulence genes were colV (90.0%), fyuA (75.0%) and vat (42.5%). Mice injected with G4-BD23 (P < 0.05) and G5-BD3 had lower survival rates than controls and visible pathological changes to lung and kidney. Nineteen MLST types were identified in 40 dairy E. coli isolates and three STs (ST10, ST48 and ST942) were shared with those from human sources. Some dairy E. coli isolates were phylogenetically related to human E. coli isolates indicating pathogenic potential.

LncRNA C9orf139 can regulate the progression of esophageal squamous carcinoma by mediating the miR-661/HDAC11 axis.

Increasing evidence has indicated that long non-coding RNAs (LncRNAs) play multiple functions in the development of cancer and function as indicators of diagnosis and prognosis. This aim of this study was to investigate the roles LncRNA C9orF139 had in the progression of esophageal squamous carcinoma (ESCC). We found C9orf139 was highly expressed in ESCC and knock down the expression of C9orf139 significantly suppressed cell proliferation, promoted apoptosis, and inhibited migration and invasion. C9orf139 was able to negatively regulate miR-661 expression. At the same time, HDAC11 expression was negatively regulated by miR-661. The C9orf139/miR-661/HDAC11 axis was further involved in regulating the expression of the NF-κB signaling pathway. The association between the C9orf139 knockdown and the reduced tumor growth and size was observed during in vivo study. C9orf139 is highly expressed in ESCC, and is thus qualified to be used as a potential diagnostic and prognostic marker for ESCC. Its promotion of ESCC progression is achieved by mediating the miR-661/HDAC11 axis.

Meta-Analysis: Shouldn't Prophylactic Corticosteroids be Administered During Cardiac Surgery with Cardiopulmonary Bypass?

Background: Corticosteroids can effectively inhibit systemic inflammation induced by cardiopulmonary bypass. Recently clinical trials and meta-analyses and current guidelines for cardiac surgery do not support corticosteroids prophylaxis during cardiac surgery because of an increase in myocardial infarction and no benefit for patients. The aim of this study is to determine whether specific corticosteroids dose ranges might provide clinical benefits without increasing myocardial infarction. Methods: The PubMed, Web of Science, Embase, Clinical Trials, and Cochrane databases were searched for randomized controlled trials (RCTs) published before August 1, 2021. Results: 88 RCTs with 18,416 patients (17,067 adults and 1,349 children) were identified. Relative to placebo and high-dose corticosteroids, low-dose corticosteroids (≤20 mg/kg hydrocortisone) during adult cardiac surgery did not increase the risks of myocardial infarction (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.43-2.17; p = 0.93). However, low-dose corticosteroids were associated with lower risks of atrial fibrillation (OR: 0.58, 95% CI: 0.44-0.76; p < 0.0001) and kidney injury (OR: 0.29, 95% CI: 0.09-0.96; p = 0.04). Furthermore, low-dose corticosteroids significantly shortened the mechanical ventilation times (mean difference [MD]: -2.74 h, 95% CI: -4.14, -1.33; p = 0.0001), intensive care unit (ICU) stay (MD: -1.48 days, 95% CI: -2.73, -0.22; p = 0.02), and hospital stay (MD: -2.29 days, 95% CI: -4.51, -0.07; p = 0.04). Conclusion: Low-dose corticosteroids prophylaxis during cardiac surgery provided significant benefits for adult patients, without increasing the risks of myocardial infarction and other complications.

Lactobacillus plantarum 17-5 attenuates Escherichia coli-induced inflammatory responses via inhibiting the activation of the NF-κB and MAPK signalling pathways in bovine mammary epithelial cells.

BACKGROUND: Mastitis is one of the most prevalent diseases and causes considerable economic losses in the dairy farming sector and dairy industry. Presently, antibiotic treatment is still the main method to control this disease, but it also brings bacterial resistance and drug residue problems. Lactobacillus plantarum (L. plantarum) is a multifunctional probiotic that exists widely in nature. Due to its anti-inflammatory potential, L. plantarum has recently been widely researched in complementary therapies for various inflammatory diseases. In this study, the apoptotic ratio, the expression levels of various inflammatory mediators and key signalling pathway proteins in Escherichia coli-induced bovine mammary epithelial cells (BMECs) under different doses of L. plantarum 17-5 intervention were evaluated. RESULTS: The data showed that L. plantarum 17-5 reduced the apoptotic ratio, downregulated the mRNA expression levels of TLR2, TLR4, MyD88, IL1ß, IL6, IL8, TNFα, COX2, iNOS, CXCL2 and CXCL10, and inhibited the activation of the NF-κB and MAPK signalling pathways by suppressing the phosphorylation levels of p65, IκBα, p38, ERK and JNK. CONCLUSIONS: The results proved that L. plantarum 17-5 exerted alleviative effects in Escherichia coli-induced inflammatory responses of BMECs.

Genome-Wide Identification of Associations of Circulating Molecules With Spontaneous Coronary Artery Dissection and Aortic Aneurysm and Dissection.

Circulating proteins play functional roles in various biological processes and disease pathogenesis. The aim of this study was to highlight circulating proteins associated with aortic aneurysm and dissection (AAD) and spontaneous coronary artery dissection (SCAD). We examined the associations of circulating molecule levels with SCAD by integrating data from a genome-wide association study (GWAS) of CanSCAD and 7 pQTL studies. Mendelian randomization (MR) analysis was applied to examine the associations between circulating molecule levels and AAD by using data from UK Biobank GWAS and pQTL studies. The SCAD-associated SNPs in 1q21.2 were strongly associated with circulating levels of extracellular matrix protein 1 (ECM1) and 25 other proteins (encoded by CTSS, CAT, CNDP1, KNG1, SLAMF7, TIE1, CXCL1, MBL2, ESD, CXCL16, CCL14, KCNE5, CST7, PSME1, GPC3, MAP2K4, SPOCK3, LRPPRC, CLEC4M, NOG, C1QTNF9, CX3CL1, SCP2D1, SERPINF2, and FN1). These proteins were enriched in biological processes such as regulation of peptidase activity and regulation of cellular protein metabolic processes. Proteins (FGF6, FGF9, HGF, BCL2L1, and VEGFA) involved in the Ras signaling pathway were identified to be related to AAD. In addition, SCAD- and AAD-associated SNPs were associated with cytokine and lipid levels. MR analysis showed that circulating ECM1, SPOCK3 and IL1b levels were associated with AAD. Circulating levels of low-density lipoprotein cholesterol and small very-low-density lipoprotein particles were strongly associated with AAD. The present study found associations between circulating proteins and lipids and SCAD and AAD. Circulating ECM1 and low-density lipoprotein cholesterol may play a role in the pathology of SCAD and AAD.

Association of Circulating Cathepsin B Levels With Blood Pressure and Aortic Dilation.

Hypertension is a key risk factor for spontaneous coronary artery dissection (SCAD) and aortic dilation. Circulating proteins play key roles in a range of biological processes and represent a major source of druggable targets. The aim of this study was to identify circulating proteins that were associated with blood pressure (BP), SCAD and aortic dilation. We identified shared genetic variants of BP and SCAD in genome-wide association studies, searched for circulating protein affected by these variants and examined the association of circulating protein levels with BP, aortic aneurysm and dissection (AAD) and aortic diameters by integrating data from circulating protein quantitative trait loci (pQTL) studies and genome wide association study (GWAS) in individuals from the UK Biobank using two-sample Mendelian randomization analysis methods. Single nucleotide polymorphisms (SNPs) in JAG1, ERI1, ULK4, THSD4, CMIP, COL4A2, FBN1, FAM76B, FGGY, NUS1, and HNF4G, which were related to extracellular matrix components, were associated with both BP and SCAD. We found 49 significant pQTL signals among these SNPs. The regulated proteins were encoded by MMP10, IL6R, FIGF, MMP1, CTSB, IGHG1, DSG2, TTC17, RETN, POMC, SCARF2, RELT, and GALNT16, which were enriched in biological processes such as collagen metabolic process and multicellular organism metabolic process. Causal associations between BP and AAD and aortic diameters were detected. Significant associations between circulating levels of cathepsin B, a well-known prorenin processing enzyme, and BP and aortic diameters were identified by using several Mendelian randomization analysis methods and were validated by independent data. Conclusion: The present study identified the association between circulating cathepsin B and BP and aortic diameters. The findings indicated that BP-associated genetic variants may influence aortic dilation risk by circulating proteins that regulate BP.

The protective effect of licochalcone A against inflammation injury of primary dairy cow claw dermal cells induced by lipopolysaccharide.

Laminitis is one of the most important and intractable diseases in dairy cows, which can lead to enormous economic losses. Although many scholars have conducted a large number of studies on laminitis, the therapeutic test of medicinal plants in vitro is really rare. Licochalcone A is proved to possess anti-inflammatory and anti-oxidant properties. But the effect of licochalcone A on LPS-induced inflammatory claw dermal cells has not been discovered yet. In this study, the primary dairy cow claw dermal cells were treated with gradient concentrations of licochalcone A (1, 5, 10 µg/mL) in the presence of 10 µg/mL lipopolysaccharides (LPS). The results indicated that licochalcone A reduced the concentrations of inflammation mediators (TNF-α, IL-1ß and IL-6), increased the activity of SOD, reduced the levels of MDA and ROS, downregulated the mRNA expressions of TLR4 and MyD88, suppressed the protein levels of p-IκBα and p-p65, and upregulated the protein expression of PPARγ. In summary, licochalcone A protected dairy cow claw dermal cells against LPS-induced inflammatory response and oxidative stress through the regulation of TLR4/MyD88/NF-κB and PPARγ signaling pathways.

Analysis of Antimicrobial Resistance and Genetic Correlations of Escherichia Coli in Dairy Cow Mastitis.

Introduction: Escherichia coli is a widespread environmental pathogen frequently causing dairy cow mastitis. This bacterium is particularly capable of acquiring antimicrobial resistance, which can have severe impacts on animal food safety and human health. The objective of the study was to investigate antimicrobial resistance and genetic correlations of E. coli from dairy cow mastitis cases in northern China. Material and Methods: Forty strains of E. coli from 196 mastitis milk samples were collected, susceptibility to 13 common antibiotics and the prevalence of resistance genes were tested in these strains, and the genetic characteristics were identified by multilocus sequence typing. Results: The results showed that most isolates were multidrug resistant (MDR) (75%), and the resistance rates to cefazolin, trimethoprim-sulfamethoxazole and ampicillin were 77.5%, 55.0%, and 52.5%, respectively. The representative genes of the isolates were aadA (62.5%) and tet(B) (60.0%). Multilocus sequence typing showed 19 different sequence types (STs) and 5 clonal complexes (CCs) in the 40 isolates, mainly represented by ST10 and CC10. The strains of the same ST or CC showed a high level of genetic relatedness, but the characteristics of their antimicrobial resistance were markedly different. Conclusion: Most E. coli isolates in the study were MDR strains. Some strains of the same ST or CC showed diverse resistance characteristics to common antimicrobials. Therefore, E. coli from dairy cow mastitis in northern China should be investigated to elucidate its antimicrobial resistance and genotypes.

Malignant plasmacytes in bone marrow detected by flow cytometry as a predictor for the risk stratification system of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a clonal disorder characterized by the proliferation of plasma cells and their accumulation within the bone marrow (BM). The flow cytometric analysis is an essential method for the hematological diseases because of high sensitivity. AIMS: This study evaluates the indication role of malignant plasmacytes (PCs) in BM detected by flow cytometry for the risk stratification of MM. METHODS: Whole BM samples from 92 newly diagnosed MM patients were included in the study. We collected 106 cells each sample by flow cytometry. Then we analyzed the correlation between the malignant PCs in BM and the characteristics of patients. RESULTS: In this study, patients were stratified according to different baseline characteristics and the median ratio of the malignant PCs were compared. The significant statistical differences (p < 0.05) were: Hb < 100 g/L versus ≥100 g/L; ß2-microglobulin <3.5 mg/dL versus 3.5-5.5 mg/dL versus >5.5 mg/dL; LDH > 250 U/L versus LDH 250 U/L; ISS I versus ISS II versus ISS III; R-ISS I versus II versus III. The detailed data are showed in Table 2. The significant correlations were observed between the malignant PCs in BM and (Figure 1): plasma cell of biopsy, hemoglobin, ß2-microglobulin, lactate dehydrogenase (LDH), creatinine. "Double hit" or "triple hit" are defined as containing any two or three of the high risk cytogenetic abnormalities (t(4;14), t(14;16), t(14;20); del17q; TP53 mutation; 1q21 gain) by mSMAR. "Double or triple hit" had independently unfavorable significance for overall survival. As expected, the malignant PCs of "double or triple hit" group is significantly higher than the group B (one high risk genetic factor) and the group A (normal cytogenetic) (p < 0.0001 and p < 0.019). CONCLUSION: Multiparametric flow cytometry is a highly sensitive method to identify and quantify malignant PCs. And the ratio of malignant PCs detected by MFC showed strongly correlation with the severity of the pathology of MM. Malignant PCs in BM detected by flow cytometry could be regarded as a predictor for the risk stratification system of MM. Thus, it should be considered applying in the routine evaluation of MM at diagnosis and after therapy.

Deferasirox combination with eltrombopag shows anti-myelodysplastic syndrome effects by enhancing iron deprivation-related apoptosis.

Iron overload (IO) affected the survival of patients with myelodysplastic syndrome (MDS). Deferasirox (DFX) is widely used in patients with MDS for iron chelation therapy, but is not suitable for MDS patients with severe thrombocytopenia. Eltrombopag (ELT) is a type of thrombopoietin receptor (TPOR) analog used in the treatment of thrombocytopenia. Therefore, we sought to explore the synergistic effects and possible mechanisms of DFX combination with ELT in MDS cells. In our study, the combination of DFX with ELT synergistically inhibited proliferation, induced apoptosis and arrested cell cycle of MDS cells. Through the RNA-sequence and gene set enrichment analysis (GSEA), iron metabolism-related pathway played important roles in apoptosis of SKM-1 cells treated with DFX plus ELT. Transferrin receptor (TFRC) was significantly highly expressed in combination group than that in single agent groups, without affecting TPOR. Furthermore, the apoptosis of the combination group MDS cells could be partially reversed by ferric ammonium citrate (FAC), accompanied with decreased expression of TFRC. These results suggested that the combination of DFX and ELT synergistically induced apoptosis of MDS cells by enhancing iron deprivation-related pathway.

BHBA regulates the expressions of lipid synthesis and oxidation genes in sheep hepatocytes through the AMPK pathway.

Pregnancy toxemia (PT) is the most frequent metabolic disease of sheep during late pregnancy, which can lead to enormous economic losses in sheep farm industry. However, the underlying mechanism of PT in sheep has not been fully elucidated. High levels of ß-hydroxy butyric acid (BHBA) exist in PT sheep. The AMP-activated protein kinase (AMPK) pathway plays a major role in regulating liver function. The aim of this study was to explore the effects of gradient concentrations of BHBA on lipid metabolism of sheep hepatocytes and the underlying molecular mechanism in vitro. The results showed that 0.6, 1.2 mmol/L BHBA could activate AMPKα, promoted the expressions of peroxisome proliferator-activated receptor alpha (PPARα) and its target genes, and inhibited the expressions of sterol regulatory element binding protein-1c (SREBP-1c) as well as its downstream genes. When the concentration of BHBA was beyond 1.2 mmol/L, the expressions of the above-mentioned proteins and genes were just the opposite. However, the expressions of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) did not change significantly. The levels of very low density lipoprotein (VLDL), triglyceride (TG) and cholesterol (T-CHOL) showed a gradually increasing trend with the increase of BHBA concentration. According to the results above, it demonstrates that high levels of BHBA can inhibit the expression of the AMPK pathway and cause lipid metabolism disorders in sheep hepatocytes, which may lead to the occurrence of PT.

Genome-Wide Identification of RNA Modifications for Spontaneous Coronary Aortic Dissection.

RNA modification plays important roles in many biological processes such as gene expression control. Genetic variants that affect RNA modification may have functional roles in aortic dissection. The aim of this study was to identify RNA modifications related to spontaneous coronary artery dissection (SCAD). We examined the association of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs) with SCAD in summary data from a genome-wide association study (GWAS) of European descent (270 SCAD cases and 5,263 controls). Furthermore, we performed expression quantitative loci (eQTL) and protein quantitative loci (pQTL) analyses for the RNAm-SNPs using publicly available data. Functional enrichment and protein-protein interaction analyses were performed for the identified proteins. We found 11,464 unique RNAm-SNPs in the SCAD GWAS dataset, and 519 were nominally associated with SCAD. Nine RNAm-SNPs were associated with SCAD at p < 0.001, and among them, seven were N6-methyladenosine (m6A) methylation-related SNPs, one (rs113664950 in HLA-DQB1) was m7G-associated SNP, and one [rs580060 in the 3'-UTR of Mitochondrial Ribosomal Protein S21 (MRPS21)] was A-to-I modification SNP. The genome-wide significant SNP rs3818978 (SCAD association p = 5.74 × 10-10) in the 5'-UTR of MRPS21 was related to m6A modification. These nine SNPs all showed eQTL effects, and six of them were associated with circulating protein or metabolite levels. The related protein-coding genes were enriched in specific Gene Ontology (GO) terms such as extracellular space, extracellular region, defense response, lymphocyte migration, receptor binding and cytokine receptor binding, and so on. The present study found the associations between RNAm-SNPs and SCAD. The findings suggested that RNA modification may play functional roles in SCAD.

Identification of potential core genes in esophageal carcinoma using bioinformatics analysis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common human malignancy worldwide. The tumorigenesis mechanism in ESCC is unclear. MATERIALS AND METHODS: To explore potential therapeutic targets for ESCC, we analyzed 3 microarray datasets (GSE20347, GSE38129, and GSE67269) derived from the gene expression omnibus (GEO) database. Then, the GEO2R tool was used to screen out differently expressed genes (DEGs) between ESCC and normal tissue. Gene ontology function and kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the database for annotation, visualization and integrated discovery to identify the pathways and functional annotation of DEGs. Protein-protein interaction of these DEGs was analyzed based on the search tool for the retrieval of interacting genes database and visualized by Cytoscape software. In addition, we used encyclopedia of RNA interactomes (ENCORI), gene expression profiling interactive analysis (GEPIA), and the human protein atlas to confirm the expression of hub genes in ESCC. Finally, GEPIA was used to evaluate the prognostic value of hub genes expression in ESCC patients and we estimated the associations between hub genes expression and immune cell populations (B Cell, CD8+ T Cell, CD4+ T Cell, Macrophage, Neutrophil, and Dendritic Cell) in esophageal carcinoma (ESCA) using tumor immune estimation resource (TIMER). RESULTS: In this study, 707 DEGs (including 385 upregulated genes and 322 downregulated genes) and 6 hub genes (cyclin B1 [CCNB1], cyclin dependent kinase 1 [CDK1], aurora kinase A [AURKA], ubiquitin conjugating enzyme E2C [UBE2C], cyclin A2 [CCNA2], and cell division cycle 20 [CDC20]) were identified. All of the 6 hub genes were highly expressed in ESCC tissues. Among of them, only CCNB1 and CDC20 were associated with stage of ESCC and all of them were not associated with survival time of patients. CONCLUSION: DEGs and hub genes were confirmed in our study, providing a thorough, scientific and comprehensive research goals for the pathogenesis of ESCC.

Angelica polysaccharide attenuates LPS-induced inflammation response of primary dairy cow claw dermal cells via NF-κB and MAPK signaling pathways.

BACKGROUND: Laminitis, an inflammation of the claw laminae, is one of the major causes of bovine lameness, which can lead to enormous economic losses and animal welfare problems in dairy farms. Angelica polysaccharide (AP) is proved to possess anti-inflammatory properties. But the role of AP on inflammatory response of the claw dermal cells has not been reported. The aim of this study was to investigate the anti-inflammatory effects of AP on lipopolysaccharide (LPS)-induced primary claw dermal cells of dairy cow and clarify the potential mechanisms. In the current research, the primary claw dermal cells were exposed to gradient concentrations of AP (10, 50, 100 µg/mL) in the presence of 10 µg/mL LPS. The levels of cytokines and nitric oxide (NO) were detected with ELISA and Griess colorimetric method. The mRNA expressions of TLR4, MyD88 and chemokines were measured with qPCR. The activation of NF-κB and MAPK signaling pathways was detected with western blotting. RESULTS: The results indicated that AP reduced the production of inflammatory mediators (TNF-α, IL-1ß, IL-6 and NO), downregulated the mRNA expression of TLR4, MyD88 and some pro-inflammatory chemokines (CCL2, CCL20, CXCL2, CXCL8, CXCL10), and suppressed the NF-κB and MAPK signaling pathways evidenced by inhibition of the phosphorylation of IκBα, p65 and ERK, JNK, p38. CONCLUSIONS: Our results demonstrated that AP may exert its anti-inflammatory effects on claw dermal cells of dairy cow by regulating the NF-κB and MAPK signaling pathways.

Effect of magnesium ammonium phosphate on the expression of adhesion molecules in sheep renal tubular epithelial cells.

Adhesion molecules play an important role in urinary calculus formation. The expressions of adhesion molecules in renal tubular has been reported in some animals. However, the role of adhesion molecules in the process of sheep urinary calculus formation is still unclear. The magnesium ammonium phosphate (MAP) is the main component of sheep urinary calculus. In this paper, the sheep renal tubular epithelial cells (RTECs) were isolated and treated with MAP, the expressions of osteopontin (OPN), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and apoptosis-related indicators caspase-3, Bcl-2 and Bax in RTECs were observed, the viability of RTECs was detected by Cell Counting Kit-8 (CCK-8). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA), and the expressions of inflammatory factors Interleukin-6 (IL-6), Interleukin-1 (IL-1), Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent (ELISA). The histopathological observation of kidney in urolithiasis sheep was made. The results showed that MAP could reduce the viability and SOD activity, enhance the activity of MDA significantly and promote the expressions of IL-1, IL-6, IL-17 and TNF-α of RTECs. By western blot and qPCR methods, the expressions of ICAM-1, VCAM-1 and OPN increased in 48 h. In addition, the expression of caspase-3 increased significantly and the ratio of Bcl-2/Bax reduced with exposure to MAP. The renal tissue structure was seriously damaged, the RTECs in urolithiasis sheep were degenerative and necrotic.

Efficacy and safety of corticosteroids prophylaxis in cardiac surgery: A protocol for systematic review and meta-analysis.

BACKGROUND: Although corticosteroid prophylaxis in adult cardiac surgery has been studied extensively for 40 years, its role remains controversial, and the optimal dose remains uncertain. The objective of this meta-analysis was to estimate the clinical benefits and risks of corticosteroid use in cardiopulmonary bypass. METHODS: We will search Pubmed, Web of Science, Embase, Clinical Trials, and Cochrane Central Register of Controlled Trials for relevant clinical trials published in any language before August 1, 2020. Randomized controlled trials (RCTs) of interest which meet inclusion criteria published or unpublished will be included. We will divide the included studies into child and adult groups for analysis. If sufficient data are available, the included trials will be divided into 4 subgroups: ≤20 mg/kg (low dose), 20-40 mg/kg (slightly high dose), 40-100 mg/kg (high dose), and >100 mg/kg (ultra high dose) based on the equivalent hydrocortisone dose. INPLASY registration number: INPLASY2020100044. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will compare the efficacy of tprophylactic corticosteroids for adults and children undergoing cardiac surgery with CPB. Due to the nature of the disease and intervention methods, randomized controlled trials may be inadequate, and we will carefully consider inclusion in high-quality, non-randomized controlled trials, but this may result in high heterogeneity and affect the reliability of the results.