Identification and Validation of a Novel Anoikis-Related Gene Signature for Predicting Survival in Patients With Serous Ovarian Cancer.

Background: Ovarian cancer is an extremely deadly gynecological malignancy, with a 5-year survival rate below 30%. Among the different histological subtypes, serous ovarian cancer (SOC) is the most common. Anoikis significantly contributes to the progression of ovarian cancer. Therefore, identifying an anoikis-related signature that can serve as potential prognostic predictors for SOC is of great significance. Methods: We intersected 308 anoikis-related genes (ARGs) and identified those significantly associated with SOC prognosis using univariate Cox regression. A LASSO Cox regression model was constructed and evaluated using Kaplan-Meier and receiver operating characteristic (ROC) analyses in TCGA (The Cancer Genome Atlas) and GSE26193 cohorts. We conducted quantitative real-time polymerase chain reaction (qPCR) to assess mRNA levels and applied bioinformatics to investigate the correlation between risk groups and gene expression, mutations, pathways, tumor immune microenvironment (TIME), and drug sensitivity in SOC. Results: Among 308 ARGs, 28 were significantly associated with SOC prognosis. A 13-gene prognostic model was established through LASSO Cox regression in TCGA cohort. High-risk group had poorer prognosis than low-risk group (median overall survival (mOS): 34.2 vs. 57.1 months, hazard ratio (HR): 2.590, 95% confidence interval (CI): 0.159 - 6.00, P < 0.001). The area under the curve (AUC) values of 0.63, 0.65, and 0.74 reflected the predictive performance for 3-, 5-, and 8-year overall survival (OS) in GSE26193 validation cohort. Functional enrichment, pathway analysis, and TIME analysis identified distinct characteristics between risk groups. Drug sensitivity analysis revealed potential drug advantages for each group. Furthermore, qPCR validation once again confirmed the effectiveness of the risk model in SOC patients. Conclusions: We developed and validated a robust ARG model, which could be used to predict OS in SOC patients. By systematically analyzing the correlation between the risk score of the ARGs signature model and various patterns, including the TIME and drug sensitivity, our findings suggest that this prognostic model contributes to the advancement of personalized and precise therapeutic strategies. Nevertheless, further validation studies and investigations into the underlying mechanisms are warranted.

Chiral-Boron-Complex-Catalyzed Asymmetric [3 + 2] Cycloaddition of ß-Trifluoromethyl α,ß-Unsaturated Ketones with N,N'-Cyclic Azomethine Imines.

The (R)-3,3'-(3,5-(CF3)2-C6H3)2-BINOL-boron-complex-catalyzed asymmetric 1,3-dipolar cycloaddition of ß-trifluoromethyl α,ß-unsaturated ketone with N,N'-cyclic azomethine imines was developed to afford N,N'-bicyclic pyrazolidine derivatives bearing a stereogenic carbon center containing CF3 motifs in high yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, and >99% ee). This catalytic system features mild reaction conditions, high efficiency, and a broad substrate scope.

Correlation between the Level of Inflammatory Cytokines and Prognosis in Children with IVIG-sensitive Kawasaki Disease and IVIG-resistant Kawasaki Disease.

Objectives: To investigate whether the levels of interleukin 1ß (IL-1ß), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) in children with Kawasaki disease (KD) are correlated with coronary artery lesion (CAL) and resistance to intravenous immunoglobulin (IVIG) treatment. Methods: A total of 216 children in line with KD diagnostic criteria were continuously included as subjects, and 50 healthy children at the same period were selected as the control group, and their levels of IL-1ß, IFN-γ, and TNF-α were detected. Results: Subjects were subdivided according to the presence or absence of CAL: 42 cases (19.4%) of 216 children with KD developed CAL and were subdivided into the CAL group, while 174 (80.6%) of those who did not develop CAL were subdivided into the NCAL group. The levels of IL-1ß, IFN-γ, and TNF-α in the CAL group and the NCAL group were higher than those in the control group (P<0.05), and the levels of those in the CAL group were higher than those in the NCAL group (P<0.05). Subjects were subdivided according to the effect of IVIG treatment: 194 cases (89.8%) of 216 children with KD had a good control of inflammation after the initial IVIG treatment, and were considered to have IVIG-sensitive KD and divided into the IVIG-sensitive group; 22 cases (10.2%) could not get good control of inflammation after the initial IVIG treatment, and were considered to have IVIG-resistant KD and divided into the IVIG-resistant group. The levels of IL-1ß, IFN-γ, and TNF-α in the IVIG-sensitive group and the IVIG-resistant group were higher than those in the control group; The levels of IL-1ß, IFN-γ, and TNF-α in the IVIG-resistant group were higher than those in the IVIG-sensitive group (P<0.05), while the fever time of the IVIG-sensitive group was lower than that of the IVIG-resistant group (P<0.05). Conclusion: Children with KD may experience changes in IL-1ß, IFN-γ, and TNF-α levels in the acute phase. Such a significant increase in levels may be a risk factor for CAL and resistance to IVIG treatment in children with KD, while the prolonged fever time is a risk factor for resistance to IVIG treatment in children with KD.

The Neuropeptide-Related HERC5/TAC1 Interactions May Be Associated with the Dysregulation of lncRNA GAS5 Expression in Gestational Diabetes Mellitus Exosomes.

OBJECTIVE: The goal of this work was to look at the expression and probable role of exosomal long noncoding RNA (lncRNA) GAS5 in gestational diabetes mellitus (GDM), as well as forecast the importance of its interaction with neuropeptides in the progression of the disease. METHODS: We divided 44 pregnant women visiting the obstetric outpatient clinics at the Affiliated Hospital of Guilin Medical College from January 2021 to December 2021 into healthy and GDM groups. We measured the expression levels of the lncRNA GAS5 in peripheral blood using PCR and compared the expression levels between the 2 groups. The Gene Expression Omnibus (GEO) database and the R software were used to analyse the differences in the genes expressed in the amniotic fluid cells in the GDM and normal groups. catRAPID was used to identify potential target proteins for GAS5. Key neuropeptide-related proteins and potential target proteins of GAS5 were extracted, and protein interaction networks were mapped. AlphaFold 2 was used to predict the structure of the target protein. The ClusPro tool was used to predict protein-protein interactions. ZDOCK was used to further confirm the protein-nucleic acid docking. RESULTS: The lncRNA GAS5 was downregulated in the peripheral blood of pregnant women with GDM compared with normal pregnant women. The subcellular localization sites of GAS5 were the nucleus, cytoplasm, and ribosome; in addition, GAS5 was present in exosomes. Intercellular interactions, including neuropeptide receptors, were increased in the amniotic fluid cells of patients with GDM. Venn diagram analysis yielded seven neuropeptide-related proteins and three GAS5 target proteins. Among them, HERC5/TAC1 interacted and GAS5 docked well with HERC5. CONCLUSION: The lncRNA GAS5 in the peripheral blood exosomes in patients with GDM may be a new target for the detection of GDM, and the interaction between GAS5 and HERC5/TAC1 may be involved in the pathogenesis of GDM.

Transcriptomic analysis of chicken immune response to infection of different doses of Newcastle disease vaccine.

Newcastle disease virus (NDV) is a contagious poultry paramyxovirus, leading to substantial economic losses to the poultry industry. Here, RNA-seq was carried out to investigate the altered expression of immune-related genes in chicken thymus within 96 h in response to NDV infection. In NDV-infected chicken thymus tissues, comparative transcriptome analysis revealed 1386 differentially expressed genes (DEGs) at 24 h with 989 up- and 397 down-regulated genes, 728 DEGs at 48 h with 567 up- and 161 down-regulated genes, 1514 DEGs at 72 h with 1016 up- and 498 down-regulated genes, and 1196 DEGs at 96 h with 522 up- and 674 down-regulated genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these candidate targets mainly participate in biological processes or biochemical, metabolic and signal transduction processes. Notably, there is large enrichment in biological processes, cell components and metabolic processes, which may be related to NDV pathogenicity. In addition, the expression of five immune-related DEGs identified by RNA-seq was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Our results indicated that the expression levels of AvBD5, IL16, IL22 and IL18R1 were obviously up-regulated, and Il-18 expression was also changed, but not significantly, which play key roles in the defense against NDV. Overall, we identified several candidate targets that may be involved in the regulation of NDV infection, which provide new insights into the complicated regulatory mechanisms of virus-host interactions, and explore new strategies for protecting chickens against the virus.

Decreased synovial fluid ghrelin levels are linked with disease severity in primary knee osteoarthritis patients and are increased following laser therapy.

BACKGROUND: Ghrelin has been proved to inhibit inflammation and promote cartilage growth. So far, its role in patients with primary knee osteoarthritis has not been investigated. OBJECTIVE: The current study was performed to explore the serum and synovial ghrelin levels as well as the relationship between ghrelin levels and disease severity in primary knee OA patients. METHODS: 52 primary knee OA patients were recruited in the study. 52 sex and age-matched patients visiting our hospital for regular body check were selected as controls. The serum and synovial fluid ghrelin levels were examined by enzyme linked immunosorbent assay (ELISA) before treatment, one week and four weeks after laser therapy, respectively. The inflammation markers IL-6 and TNF-α were also investigated. The radiographic progression was assessed by Kellgren-Lawrence (K-L) grade scale and the symptomatic severity was evaluated by visual analog scale (VAS), Lequesne index and Lysholm scores. The Receiver Operating Characteristic (ROC) analysis curve was conducted to test the diagnostic value of ghrelin, IL-6 and TNF-α for radiographic progression. RESULTS: No significant difference of serum ghrelin levels was found between knee OA patients and healthy controls. Synovial fluid ghrelin concentrations were significantly negatively correlated with K-L grading (r=-0.591, P<0.001).Attenuated synovial fluid ghrelin levels were also related to clinical severity determined by Lequesne index (r=-0.308, P=0.025),VAS scores (r=-0.591, P<0.001) and Lysholm scores (r=0.381, P=0.005).In addition, ghrelin levels were also negatively associated with TNF-α (r=-0.424, P=0.002) and IL-6 concentrations (r=-0.428, P=0.002). ROC curve analysis demonstrated that ghrelin exhibited more diagnostic value than IL-6 and TNF-α for assessing radiographic progression in medium-late stage. CONCLUSIONS: Decreased synovial fluid ghrelin levels are related to disease severity in patients with primary osteoarthritis and are increased following laser therapy. Local application of ghrelin may serve as an adjunctive therapy for knee OA.