Toll-like receptors (TLRs) play crucial roles in the recognition of invading pathogens and the immune system. However, the effect of TLRs in asthma is still not fully known. This study was performed to better understand the role of TLR signatures in asthma. Blood samples from case–control studies (study 1: 348 asthmas and 39 normal controls and validation study 2: 411 asthmas and 87 normal controls) were enrolled. The single-sample gene set enrichment analysis method was performed to quantify the abundance of 21 TLR signatures. Gene ontology analysis and pathway function analysis were conducted for functional analysis, and a protein–protein interaction network was constructed. The area under the curve (AUC) value was used to assess the diagnostic capacity. In this study, TLR2/TLR3/TLR4 pathway, MyD88-dependent/independent TLR pathway, positive regulation of TLR4 pathway, and TLR binding signatures were significantly higher in asthma. Functional analysis showed that biological processes and pathways were still involved in TLR cascades and TLR signaling pathway. Eleven hub TLR-related genes were identified, and further validation demonstrated that the combination of TLR-related genes was a good diagnostic biomarker for asthma (AUC = 0.8). Our study provided more insight into the underlying immune mechanism of how TLR signatures affected asthma. The use of the easy-to-apply TLR-related genes might represent a promising blood-based biomarker for early detection of asthma.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is increasing in incidence. Local ablative therapy plays a leading role in HCC treatment. Radiofrequency (RFA) is one of the first-line therapies for early local ablation. Other local ablation techniques (e.g., microwave ablation, cryoablation, irreversible electroporation, phototherapy.) have been extensively explored in clinical trials or cell/animal studies but have not yet been established as a standard treatment or applied clinically. On the one hand, single treatment may not meet the needs. On the other hand, ablative therapy can stimulate local and systemic immune effects. The combination strategy of immunotherapy and ablation is reasonable. In this review, we briefly summarized the current status and progress of ablation and immunotherapy for HCC. The immune effects of local ablation and the strategies of combination therapy, especially synergistic strategies based on biomedical materials, were discussed. This review is hoped to provide references for future researches on ablative immunotherapy to arrive to a promising new era of HCC treatment.
The diagnosis of paraduodenal hernia is still a challenge in clinical practice due to lacking of specific symptoms. Case presentation: An 83-yr-old male patient presented to our department due to severe abdominal pain for 8 h. Abdominal contrast enhanced computerized tomography (CT) scan indicated intussusception in the duodenum and the upper segment of jejunum, as well as internal hernia. He complaint of progression in the abdominal pain, and then laparoscope was carried out, which indicated left-sided paraduodenal hernia. Subsequently, the patient was transferred to celiotomy, during which slight ischemic changes were noticed in the intestinal canal. Meanwhile, a hernial orifice was noticed in the left orifice of the duodenum. Conclusions: In this case, we presented our experiences on the diagnosis of paraduodenal hernia and intussusception. Our study contributed to the understanding, early diagnosis and selection of surgical options for the surgeons.
The detection of DNA methyltransferase (MTase) was crucial for understanding gene expression regulation, cancer mechanisms, and various biological processes, contributing significantly to disease diagnosis and drug development. Herein, a nanopore sensor based on cascaded signal amplification of DNA walker and autocatalytic hybridization reaction (AHR) was developed for the ultrasensitive determination of various MTases. In the presence of Dam MTase, the hairpin structure H
Background and Aims: Titanium dioxide nanoparticles (TiO2 NPs) have been reported to induce liver injury in animal experiments, possibly due to oxidative stress and inflammation. Ellagic acid (EA) is a dietary polyphenol extracted from natural sources and possesses antioxidant and anti-inflammatory properties. However, the potential of EA to alleviate TiO2 NP-induced liver injury remains unclear.Methods: Primary hepatocytes and L02 cells were cultured in the presence of 45 μM EA and 10 μg/ml TiO2 NPs. Mice were orally administered TiO2 NPs (150 mg/kg) and EA (50 mg/kg) for eight weeks. RNA-sequencing (RNA-seq) was used to investigate the mechanisms underlying oxidative stress, inflammation, and liver fibrosis.Results: We evaluated the effects of EA on cytotoxicity, oxidative stress in hepatocytes, inflammation, and fibrosis in mice exposed to TiO2 NPs for an extended period. Our findings indicated that EA had a protective effect on TiO2 NP-exposed hepatocytes, reducing cytotoxicity, oxidative stress, and inflammation. Furthermore, EA treatment significantly decreased serum aminotransferase levels in TiO2 NP-exposed mice. In addition, EA treatment significantly reduced hepatic stress response, inflammatory cell infiltration, and hepatic fibrosis in mice. In vitro and in vivo mechanistic studies revealed that the protective effects of EA were mediated by the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), which EA promoted the translocation of Nrf2 from cytosolic to nuclei, as indicated by the finding that Nfe2l2 shRNA and inhibition of Nrf2 by ML385 reversed the EA-induced hepatoprotective effects in TiO2 NP-exposed hepatocytes and mice.Conclusion: EA ameliorates long-term TiO2 NP exposure-induced hepatic oxidative stress, inflammation, and fibrosis in mice dependent on Nrf2 activation. As a potential Nrf2 activator, EA is a promising candidate for the treatment of TiO2 NP-induced liver injury.Funding: This study was supported by Zhejiang Provincial Natural Science Foundation of China [No. LY23H030002], Zhejiang Provincial Medical and Health Science and Technology Project [No. 2023KY412], Zhejiang Province Public Welfare Technology Application Research Project [No. LGF21H16002], Liver Cancer Early Warning and Early Intervention Technology Innovation Team of Taizhou Central Hospital (Taizhou Universtiy Hospital).Declaration of Interest: The authors declare no conflict of interest.Ethical Approval: Animal experiments were conducted in accordance with guidelines established by the Institutional Animal Care and Use Committee of Taizhou University, China. The study protocol was approved by the Ethics Committee for Medical Laboratory Animals of the Taizhou University.
Introduction: Despite the widespread use of general anaesthetics, the mechanisms mediating their effects are still not understood. Although suppressed in most parts of the brain, neuronal activity, as measured by FOS activation, is increased in the hypothalamic supraoptic nucleus (SON) by numerous general anaesthetics, and evidence points to this brain region being involved in the induction of general anaesthesia and natural sleep. Posttranslational modifications of proteins, including changes in phosphorylation, enable fast modulation of protein function which could be underlying the rapid effects of general anaesthesia. In order to identify potential phosphorylation events in the brain mediating general anaesthesia effects, we have explored the phosphoproteome responses in the rat SON, and compared these to cingulate cortex (CC) which displays no FOS activation is response to general anaesthetics. Methods: Adult Sprague-Dawley rats were treated with isoflurane for 15 minutes. Proteins from the CC and SON were extracted and processed for Nano-LC Mass Spectrometry (LC-MS/MS). Phosphoproteomic determinations were performed by LC-MS/MS. Results: We found many changes in the phosphoproteomes of both the CC and SON in response to 15 minutes of isoflurane exposure. Pathway analysis indicated that proteins undergoing phosphorylation adaptations are involved in cytoskeleton remodelling and synaptic signalling events. Importantly, changes in protein phosphorylation appeared to be brain region-specific suggesting that differential phosphorylation adaptations might underlie the different neuronal activity responses to general anaesthesia between the CC and SON. Conclusion: In summary, these data suggest that rapid posttranslational modifications in proteins involved in cytoskeleton remodelling and synaptic signalling events might mediate the central mechanisms mediating general anaesthesia.
Abstract Long noncoding RNAs (lncRNAs) show multiple functions, including immune response. Recently, the immune‐related lncRNAs have been reported in some cancers. We first investigated the immune‐related lncRNA signature as a potential target in hepatocellular carcinoma (HCC) survival. The training set ( n = 368) and the independent external validation cohort ( n = 115) were used. Immune genes and lncRNAs coexpression were constructed to identify immune‐related lncRNAs. Cox regression analyses were perfumed to establish the immune‐related lncRNA signature. Regulatory roles of this signature on cancer pathways and the immunologic features were investigated. The correlation between immune checkpoint inhibitors and this signature was examined. In this study, the immune‐related lncRNA signature was identified in HCC, which could stratify patients into high‐ and low‐risk groups. This immune‐related lncRNA signature was correlated with disease progression and worse survival and was an independent prognostic biomarker. Our immune‐related lncRNA signature was still a powerful tool in predicting survival in each stratum of age, gender, and tumor stage. This signature mediated cell cycle, glycolysis, DNA repair, mammalian target of rapamycin signaling, and immunologic characteristics (i.e., natural killer cells vs. Th1 cells down, etc). This signature was associated with immune cell infiltration (i.e., macrophages M0, Tregs, CD4 memory T cells, and macrophages M1, etc.,) and immune checkpoint blockade (ICB) immunotherapy‐related molecules (i.e., PD‐L1, PD‐L2, and IDO1). Our findings suggested that the immune‐related lncRNA signature had an important value for survival prediction and may have the potential to measure the response to ICB immunotherapy. This signature may guide the selection of the immunotherapy for HCC.
Hepatocellular carcinoma (HCC) is closely associated with the immune microenvironment. To identify the effective population before administering treatment, the establishment of prognostic immune biomarkers is crucial for early HCC diagnosis and treatment.A total of 335 IRGs identified from 788 overlapping IRGs were associated with the survival of HCC. A prognostic immunoscore model was identified. The Kaplan-Meier survival curves and time-dependent ROC analysis revealed a powerful prognostic performance of immunoscore signature via multi validation. Besides, the immunoscore signature exhibited a better predictive power compared to other prognostic signatures. Gene set enrichment analysis showed multiple signaling differences between the high and low immunoscore group. Furthermore, immunoscore was significantly associated with multiple immune cells and immune infiltration in the tumor microenvironment.We identified the immunoscore as a robust marker for predicting HCC patient survival.Three sets of immune-related genes (IRGs) were integrated to identify the overlapping IRGs. Weighted gene co-expression network analysis was performed to obtain the survival-related IRGs. Further, the prognostic immunoscore model was constructed via LASSO-penalized Cox regression analysis. Then the prognostic performance of immunoscore was evaluated. In addition, ESTIMATE and CIBERSORT algorithms were applied to explore the relationship between immunoscore and tumor immune microenvironment.
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