Abstract Background Cerebral resuscitation determines the prognosis for patients who have experienced sudden death, and brain protection is the focus of clinical treatment. Cerebral resuscitation depends on the timing and quality of cardiopulmonary resuscitation (CPR). At present, cerebral oxygen monitoring is used mainly to monitor the quality of external cardiac compression and provide a prognosis for the nervous system. However, after the return of autonomous circulation, it is necessary to conduct continuous monitoring to ensure measures are taken timeously since hemodynamic instability, brain edema, and other factors may cause occult brain injury, and invasive arterial pressure cannot represent cerebral perfusion. Case presentation By using continuous cerebral oxygen monitoring after CPR and the return of spontaneous circulation, a patient who was witnessed to have experienced sudden death in the hospital was found to have insufficient cerebral perfusion; he underwent timely intra-aortic balloon counterpulsation to improve his hemodynamics and cerebral perfusion. The patient went on to achieve a good neurological prognosis. Conclusion Cerebral oxygen monitoring should be conducted throughout the treatment period; physicians should understand cerebral perfusion in real time and implement timely intervention measures to reduce occult brain injury and improve the neurological prognosis of patients.
Abstract Background N6-methyladenosine (m 6 A) RNA methylation is the most common chemical decoration in mammalian RNAs which exerts vital effects on numerous cellular processes. Recently, m 6 A regulators have been validated to participate in promoting immune evasion and act as prognostic factors in various cancers. Nevertheless, the predictive abilities of m 6 A regulators for the prognosis and immunotherapy response in gastric cancer (GC) remain indistinct. Methods Herein, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, The Human Protein Atlas (HPA), and a clinical GC cohort were applied for differential expression analysis, correlation analysis, survival analysis, and hazard model construction. Consensus clustering analysis was performed to authenticate the PD-L1 (CD274) expression, stemness features, immune cell infiltration, and tumor microenvironment (TME) in GC individuals. Furthermore, protein-protein interaction, immunotherapy response prediction, and drug susceptibility prediction were performed, respectively. Additionally, tissue microarray (TMA), immunohistochemical staining, western blot assay, Transwell assay, and flow cytometry assay were adopted to evaluate the protein expression, the prognostic value, and the influence of FTO on GC malignant phenotypes as well as the expression of PD-L1. Results In agreement with the majority of m 6 A regulators, FTO was overexpressed and predicted poor prognosis in GC. Based on consensus clustering analysis, two independent subgroups (G1/G2) were identified. Notably, FTO was upregulated in the G1 subgroup. Meanwhile, the infiltration level of CD8+ T cells was strikingly decreased while the stemness features were enhanced in the G1 subgroup. More importantly, FTO was negatively correlated with microsatellite instability (MSI) and tumor mutation burden (TMB). Furthermore, immune checkpoint blockade (ICB) response prediction indicated that patients with upregulated FTO showed high tumor immune dysfunction and exclusion (TIDE) scores. Subsequently, FTO was confirmed to be related to multiple immune checkpoints, particularly PD-L1. Specifically, FTO was dramatically upregulated in GC cell lines and clinical cancer samples. Functional experiments illustrated that FTO acted as an oncogene to facilitate malignant phenotypes. Notably, PD-L1 was remarkably downregulated after RNA interference-mediated knockdown of FTO. Conclusion FTO can aggravate GC malignant phenotypes. More importantly, it could be utilized to predict the long-term prognosis and the immunotherapy response in GC individuals. However, larger trials should be performed to verify the prediction accuracy.
The inhibition of STAT3 may exert cell-autonomous cytotoxic and cytostatic effects, yet may also stimulate anticancer immunosurveillance through the neutralization of immunosuppressive circuitries. In addition, STAT3 inhibition in cancer cells may stimulate the type 1 interferon response elicited by anthracyclines. This pathway results in an enhanced chemotherapy-associated anticancer immune response with improved therapeutic efficacy. Hence, combination therapies that include immunogenic cell death (ICD) inducers and STAT3 inhibitors can be envisaged.
ABSTRACT Lung cancer is a major cause of cancer‐related mortality, and radiotherapy is often limited by tumor resistance and side effects. This study explores whether epoxymicheliolide (ECL), a compound from feverfew, can enhance radiotherapy efficacy in lung cancer. We tested ECL on A549 and PC‐9 lung cancer cell lines to evaluate its effect on x‐ray irradiation. We measured apoptosis, NF‐κB pathway inhibition, TGF‐β secretion reduction, and epithelial‐mesenchymal transition suppression. In vivo, C57BL/6 mice with lung tumors received ECL and radiotherapy. ECL enhanced the antiproliferative effects of x‐ray irradiation, induced apoptosis in senescent cells, inhibited the NF‐κB pathway, reduced TGF‐β levels, and suppressed epithelial‐mesenchymal transition. ECL also inhibited tumor growth and improved survival in mice. ECL is a promising adjunct to radiotherapy for lung cancer, improving treatment outcomes by targeting multiple tumor progression mechanisms. It offers potential for enhanced management of lung cancer.
SHIP2 is a multi-domain inositol 5-phosphatase binding to a variety of phosphotyrosine (pY)-containing proteins through its SH2 domain, so as to regulate various cell signaling pathways by modulating the phosphatidylinositol level in the plasma membrane. Unfavorably, Helicobacter pylori can hijack SHIP2 through the CagA protein to induce gastric cell carcinogenesis. To date, the interaction between SHIP2 and CagA was not analyzed from a structural point of view. Here, the binding of SHIP2-SH2 with Tyr-phosphorylated peptides from four EPIYA motifs (A/B/C/D) in CagA was studied using NMR spectroscopy. The results showed that EPIYA-C and -D bind to a similar interface of SHIP2-SH2, including a pY-binding pocket and a hydrophobic pocket, to achieve high affinity, while EPIYA-A and -B bind to a smaller interface of SHIP2-SH2 with weak affinity. By summarizing the interface and affinity of SHIP2-SH2 for CagA EPIYA-A/B/C/D, c-MET and FcgR2B ITIM, it was proposed that, potentially, SHIP2-SH2 has a selective preference for L > I > V for the aliphatic residues at the pY+3 position in its ligand. This study reveals the rule of the ligand sequence bound by SHIP2-SH2 and the mechanism by which CagA protein hijacks SHIP2, which will help design a peptide inhibitor against SHIP2-SH2.
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